Science.gov

Sample records for anticholinergic drugs scopolamine

  1. The antidepressant effects of anticholinergic drugs.

    PubMed

    Howland, Robert H

    2009-06-01

    Acetylcholine is a neurotransmitter that is important for communication between neurons and muscle, is involved in direct neurotransmission in the autonomic parasympathetic nervous system, and has been implicated in cognitive processing, arousal, and attention in the brain. The cholinergic-adrenergic hypothesis of mood disorders states that a given affective state might represent a balance between central cholinergic and adrenergic neurotransmitter activity in those areas of the brain regulating moods. According to this hypothesis, depression would be the clinical manifestation of a state of cholinergic dominance, whereas mania would reflect adrenergic dominance. On the basis of this hypothesis, anticholinergic drugs have been investigated as potential treatments for depression, but study results have not shown consistent antidepressant effects. However, the dosage dependency of scopolamine's effect across different studies and the lack of antidepressant effects with other anticholinergic drugs suggest that a specific muscarinic receptor subtype might be most relevant to the potential antidepressant mechanism of action of anticholinergic drugs.

  2. Comparative study on pharmacokinetics of a series of anticholinergics, atropine, anisodamine, anisodine, scopolamine and tiotropium in rats.

    PubMed

    Tian, Fengjie; Li, Cuiyun; Wang, Xin; Ren, Shuangxia; Li, Ning; Liu, Qi; Zhou, Sufeng; Lu, Yang; Zhao, Di; Chen, Xijing

    2015-09-01

    The compound series of traditional anticholinergics [atropine (Atr), anisodamine (Ani), anisodine (AT3), and scopolamine (Sco)], naturally occurring belladonna alkaloid, have been approved for numerous therapeutic uses since 1970s. Tiotropium, a novel M receptor antagonist for the treatment of chronic obstructive pulmonary disease, was structurally modified based on atropine-like drugs. Clinical phenomena suggested that the changes of substituent group were related to the pharmacokinetic and pharmacodynamic characteristics of the agents. In an attempt to compare the pharmacokinetics of the series of anticholinergics and investigate the subsets motivating selective anticholinergic potencies, a sensitive LC-MS/MS method was established to analyze the differences of pharmacokinetic parameters. In this paper, we determined the pharmacokinetics of atropine, anisodamine, anisodine, scopolamine, and tiotropium after i.v. and i.g. single dose administration. After i.v. administration, the maximum drug plasma concentrations (C max) of Atr, Ani, AT3, and Sco were 274.25 ± 53.66, 267.50 ± 33.16, 340.50 ± 44.52, and 483.75 ± 78.13 ng/mL. Tiotropium had a slightly higher area under the curve with a significant increase of C max value. Because of their partial solubility, Atr, Ani, AT3, and Sco had different bioavailability in rats of 21.62, 10.78, 80.45 and 2.52 %, respectively. Following i.g. administration of tiotropium, the C max value below 20 ng/mL revealed the very low oral absorption. The urinary excretion rates of Atr, Ani, AT3, Sco and tiotropium were 11.33, 54.86, 32.67, 8.69 and 73.91 %. This work provided relatively comprehensive preclinical data on the series of anticholinergics, which may be used to explain the clinical adverse effects and applications.

  3. Anticholinergic drugs--functional antidotes for the treatment of tabun intoxication.

    PubMed

    Krejcová, Gabriela; Kassa, Jirí

    2004-01-01

    1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun (LD50). The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. 3. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine.

  4. Study of the n-methyl-d-aspartate antagonistic properties of anticholinergic drugs

    SciTech Connect

    McDonough, J.H.; Shih, T.M.

    1995-12-31

    A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs. PHARMACOL BIOCHEM BEHAV. 51(2/3) 249-253, 1995. Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex have the ability to terminate nerve agent-induced seizures and modulate the neuropathologic consequences of agent exposure. Drugs with mixed anticholinergic and anti-NMDA properties potentially provide an ideal class of compounds for development as anticonvulsant treatments for nerve agent casualties. The present experiment evaluated the potential NMDA antagonist activity of 11 anticholinergic drugs by determining whether pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antagonized NMDA lethality and are ranked according to their potency: mecamylamine > procyclidine = benactyzine > biperiden > tribexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinudidinyl benzilate (QNB), and scopolamine failed to show NMDA antagonist properties. In addition, and unexpectedly, diazepam, ethanol, and pentobarbital were also shown to be capable of antagonizing NMDA lethality over a certain range of doses. The advantages and limitations of using antagonism of NMDA lethality in mice as a bioassay for determining the NMDA antagonist properties of drugs are also discussed.

  5. [Effect of anticholinergic drugs on cognitive impairment in the elderly].

    PubMed

    López-Álvarez, Jorge; Zea Sevilla, María Ascensión; Agüera Ortiz, Luis; Fernández Blázquez, Miguel Ángel; Valentí Soler, Meritxell; Martínez-Martín, Pablo

    2015-01-01

    The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed.

  6. Anticonvulsant Treatment of Nerve Agent Seizures: Anticholinergics versus Diazepam in Soman-Intoxicated Guinea Pigs

    DTIC Science & Technology

    2000-01-01

    8 June 1999 Abstract A total of eight anticholinergic drugs (aprophen, atropine, azaprophen, benactyzine, biperiden , procyclidine, scopolamine...procyclidine and aprophen terminated seizures most rapidly while scopolamine, trihexyphenidyl, biperiden , and diazepam were significantly slower. When...given 40 min after seizure onset, diazepam was the most potent compound tested, followed by scopolamine, benactyzine and biperiden ; atropine was not

  7. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs.

    PubMed

    Gill, Sudeep S; Mamdani, Muhammad; Naglie, Gary; Streiner, David L; Bronskill, Susan E; Kopp, Alexander; Shulman, Kenneth I; Lee, Philip E; Rochon, Paula A

    2005-04-11

    The prescribing cascade model involves the misinterpretation of an adverse reaction to 1 drug and the subsequent, potentially inappropriate prescription of a second drug. We present a new example of the prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs used to manage urinary incontinence. A population-based retrospective cohort study was carried out in Ontario, Canada. Participants included 44,884 older adults with dementia (20,491 were dispensed a cholinesterase inhibitor and 24,393 were not), enrolled between June 1, 1999, and March 31, 2002. Subjects were observed until they received an anticholinergic drug, stopped the cholinesterase inhibitor treatment, died, or the study period ended (March 31, 2003). The main outcome measure was receipt of an anticholinergic drug to manage urinary incontinence. After adjusting for potential confounding factors, we observed that older adults with dementia who were dispensed cholinesterase inhibitors had an increased risk of subsequently receiving an anticholinergic drug (4.5% vs 3.1%; P<.001; adjusted hazard ratio, 1.55; 95% confidence interval, 1.39-1.72), relative to those not receiving cholinesterase inhibitors. This finding was consistent in a series of subgroup analyses. Use of cholinesterase inhibitors is associated with an increased risk of receiving an anticholinergic drug to manage urinary incontinence. The use of an anticholinergic drug in this setting may represent a clinically important prescribing cascade. Clinicians should consider the possible contributing role of cholinesterase inhibitors in new-onset or worsening urinary incontinence and the potential risk of coprescribing cholinesterase inhibitors and anticholinergic drugs to patients with dementia.

  8. Anticholinergic Accumulation: A Slumbering Interaction between Drugs and Food Supplements.

    PubMed

    Vrolijk, Misha F; Opperhuizen, Antoon; Jansen, Eugène H J M; Bast, Aalt; Haenen, Guido R M M

    2015-12-01

    Many compounds display anticholinergic effects which might give rise to cognitive impairment and even delirium. These side effects are caused by their ability to bind to muscarinic receptors in our brain. Especially with combination of compounds, these serious effects are seen. This phenomenon, known as anticholinergic accumulation, is especially seen in the elderly. A classification of drugs for anticholinergic side effects has been made based on clinical observations, the ACB score. Here, we aimed to substantiate this classification by comparing the affinity of numerous drugs for the muscarinic receptors to the ACB score. Additionally, a number of supplements were screened. The affinity of the compounds was determined by their ability to displace the radioligand [(3)H]pirenzepine of the muscarinic receptor induced by these compounds. Our results show that the affinity of a compound for the muscarinic receptors correlated with its ACB score. Also food supplements appeared to bind to these muscarinic receptors. Moreover, several drug-drug, supplement-supplement and supplement-drug combinations had an affinity that is higher than the affinity of single compounds. This explains the phenomenon of anticholinergic accumulation. In conclusion, care should be taken to drug-drug and supplement-drug combinations with respect to anticholinergic accumulation.

  9. Perspectives on the Use of Scopolamine as an Adjunct Treatment to Enhance Survival Following Organophosphorus Nerve Agent Poisoning

    DTIC Science & Technology

    2010-11-01

    MILITARY MEDICINE, 175, 11:878,2010 Perspectives on the Use of Scopolamine as an Adjunct Treatment to Enhance Survival Following Organophosphorus...Nerve Agent Poisoning Irwin Koplovitz, RhD; Susan Schulz ABSTRACT Scopolamine (SCP) is an anticholinergic drug used clinically for decades to treat...PB is currently EDA approved only for use against soman. Scopolamine (SCP) is a well known anticholinergic drug that has been used clinically for

  10. Therapy against organophosphate poisoning: the importance of anticholinergic drugs with antiglutamatergic properties.

    PubMed

    Weissman, Ben Avi; Raveh, Lily

    2008-10-15

    Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission.

  11. Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

    SciTech Connect

    Weissman, Ben Avi Raveh, Lily

    2008-10-15

    Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission.

  12. Liquid-Spray Formulation Of Scopolamine

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Cintron, Nitza M.

    1992-01-01

    Scopolamine, fast-acting anticholinergic drug, formulated into drops administered intranasally. Formulation very useful for people who need immediate relief from motion sickness, and they can administer it to themselves. Also used in other clinical situations in which fast-acting anticholinergic medication required. Modified into such other forms as gel preparation, aqueous-base ointment, or aerosol spray or mist; also dispensed in metered-dose delivery system.

  13. Liquid-Spray Formulation Of Scopolamine

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Cintron, Nitza M.

    1992-01-01

    Scopolamine, fast-acting anticholinergic drug, formulated into drops administered intranasally. Formulation very useful for people who need immediate relief from motion sickness, and they can administer it to themselves. Also used in other clinical situations in which fast-acting anticholinergic medication required. Modified into such other forms as gel preparation, aqueous-base ointment, or aerosol spray or mist; also dispensed in metered-dose delivery system.

  14. Minimizing anticholinergic drug prescribing in older hospitalized patients: a full audit cycle

    PubMed Central

    Soiza, Roy L; Mangoni, Arduino A

    2014-01-01

    Introduction: Anticholinergic drugs are associated with poor outcomes in older patients but no specific intervention strategies aimed at reducing anticholinergic drug exposure have been described. Objectives: To identify whether a consultant-led medication review targeting anticholinergics would reduce anticholinergic drug exposure [number of anticholinergic drugs and Anticholinergic Risk Scale (ARS) score]. Methods: The first phase of the audit included 70 consecutive admissions (mean age 84 years, 53 women). ARS score was calculated on admission and after initial consultant review. Re-audit was undertaken on another 70 consecutive admissions (mean age 83 years, 43 women) after introducing a system of informing the responsible consultant of the ARS score at their first review. Results: Drugs with anticholinergic effects (n = 53) were prescribed preadmission to 45/140 (32%) of patients. Consultant geriatrician review reduced ARS scores (p = 0.01), especially following the introduction of the information system (p = 0.002). In the first arm of the audit, 51 (73%) patients had ARS of 0 after a consultant’s review compared with 47 (67%) patients on admission, whilst 67 (96%) patients had ARS of 2 or less after a consultant’s review compared with 63 (90%) patients on admission. In the second arm of the audit, 59 (84%) patients had ARS of 0 after a consultant’s review compared with 48 (69%) patients on admission, whilst 70 (100%) patients had ARS of 2 or less after a consultant’s review compared with 69 (99%) patients on admission. Anticholinergic drugs were either stopped, or their dose reduced, in 35% of patients in the first arm of the audit and in 73% of patients in the re-audit (odds ratio 5.0, 95% confidence interval 1.4–17.8). Conclusion: Consultant-led medication review (standard practice) was effective at reducing anticholinergic drug exposure in the acute setting. A system of alerting clinicians to patients prescribed anticholinergic medications

  15. Anticholinergic Drug Burden in Persons with Dementia Taking a Cholinesterase Inhibitor: The Effect of Multiple Physicians.

    PubMed

    Reppas-Rindlisbacher, Christina E; Fischer, Hadas D; Fung, Kinwah; Gill, Sudeep S; Seitz, Dallas; Tannenbaum, Cara; Austin, Peter C; Rochon, Paula A

    2016-03-01

    To explore the association between the number of physicians providing care and anticholinergic drug burden in older persons newly initiated on cholinesterase inhibitor therapy for the management of dementia. Population-based cross-sectional study. Community and long-term care, Ontario, Canada. Community-dwelling (n = 79,067, mean age 81.0, 60.8% female) and long-term care residing (n = 12,113, mean age 84.3, 67.2% female) older adults (≥66) newly dispensed cholinesterase inhibitor drug therapy. Anticholinergic drug burden in the prior year measured using the Anticholinergic Risk Scale. Community-dwelling participants had seen an average of eight different physicians in the prior year. The odds of high anticholinergic drug burden (Anticholinergic Risk Scale score ≥ 2) were 24% higher for every five additional physicians providing care to individuals in the prior year (adjusted odds ratio = 1.24, 95% confidence interval = 1.21-1.26). Female sex, low-income status, previous hospitalization, and higher comorbidity score were also associated with high anticholinergic drug burden. Long-term care facility residents had seen an average of 10 different physicians in the prior year. After a sensitivity analysis, the association between high anticholinergic burden and number of physicians was no longer statistically significant in the long-term care group. In older adults newly started on cholinesterase inhibitor drug therapy, greater number of physicians providing care was associated with higher anticholinergic drug burden scores. Given the potential risks of anticholinergic drug use, improved communication among physicians and an anticholinergic medication review before prescribing a new drug are important strategies to improve prescribing quality. © 2016 The Authors.The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  16. [Anticholinergic drugs in the therapy of obstructive airway diseases].

    PubMed

    Windt, Roland

    2011-04-01

    The anticholinergic effects from botanical preparations of the deadly nightshade family have been used for hundreds of years for the treatment of obstructive airway diseases. Nowadays, derivatives of the plant alkaloids with quaternary ammonium structure, ipratropium bromide and tiotropium bromide, are used, which retain the bronchodilator properties of the parent compounds but are much safer since they are poorly absorbed across biologic membranes. They are the bronchodilators of choice in the management of chronic obstructive pulmonary disease (COPD). However, ipratropium is considered a second-line agent in the treatment of asthma as the bronchodilatory effects seen with ipratropium are less than those seen with beta-adrenergic drugs. Tiotropium is only approved for use in COPD. Though, a recent study provides some evidence that this agent may be an alternative to long-acting beta agonists as an add-on therapy to inhaled glucocorticoids for asthma.

  17. Anticholinergic drug exposure is associated with delirium and postdischarge institutionalization in acutely ill hospitalized older patients.

    PubMed

    Egberts, Angelique; van der Craats, Saskia T; van Wijk, Melissa D; Alkilabe, Shams; van den Bemt, Patricia M L A; Mattace-Raso, Francesco U S

    2017-06-01

    Several studies investigated the possible association between anticholinergic drugs and diverse clinical outcomes in older persons, but the results are inconsistent. The aim of this study was to investigate whether anticholinergic drug exposure is associated with delirium on admission, length of hospital stay, postdischarge institutionalization and in-hospital mortality in acutely ill hospitalized older patients. In this observational chart review study, we included acutely ill patients aged 65 and older who were admitted to the geriatric ward of the Erasmus University Medical Center, Rotterdam, The Netherlands, between 2012 and 2015 (n = 905). Anticholinergic drug exposure on admission was defined as the use of anticholinergic drugs, total number of anticholinergic drugs and anticholinergic drug burden score (ADB), quantified with the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden scale (ACB) and the list of Chew et al. (Chew). Logistic regression analyses were performed to investigate possible associations between anticholinergic drug exposure and the aforementioned outcomes. Analyses were adjusted for age, sex, comorbidities, non-anticholinergic drugs and delirium, where appropriate. Moderate and high ADB measured with the ARS were associated with delirium on admission with odds ratios (OR) of 1.70 (95% confidence interval (CI) = 1.16-2.49) and 1.83 (95% CI = 1.06-3.15), respectively. High ADB measured with the ARS was also associated with postdischarge institutionalization (OR = 2.43, 95% CI = 1.24-4.75). No associations were found using the ACB and Chew. Future studies are warranted to investigate the clinical usefulness of the ARS in reducing complications in older persons.

  18. Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients

    PubMed Central

    Soiza, Roy L; Mangoni, Arduino A

    2013-01-01

    Objective: To compare associations between four measures of anticholinergic exposure (anticholinergic risk scale, ARS; anticholinergic drug burden, DBAC; number and use versus no use of anticholinergic drugs), Barthel Index (BI, physical function) and Abbreviated Mental Test (AMT, cognitive function) on admission in older hospitalized patients. Methods: Prospective observational study of a consecutive series of 271 older patients (age 83 ± 7 years) from community-dwelling and institutionalized settings, admitted to an acute geriatric admission unit between 28 September 2011 and 18 December 2011. The main outcome measures were BI quartiles (primary outcome) and AMT (secondary outcome) on admission. Results: Anticholinergic prevalence was 47%. Multinomial logistic regression showed higher DBAC was associated with a greater risk of being in the lower BI quartiles versus highest BI quartile (Q4). This risk was significant for Q3 (p = 0.04) and Q2 (p = 0.02) but not for Q1 (p = 0.06). A greater number of anticholinergic drugs was associated with a higher risk of being in Q2 (p = 0.02). This risk was not significant for either Q3 (p = 0.10) or Q1 (p = 0.06). No significant associations were observed either with use of anticholinergic medication or with ARS and BI quartiles. AMT did not show independent associations with any of the four measures of anticholinergic exposure. Conclusion: In older hospitalized patients, DBAC and some crude measures of anticholinergic exposure, but not ARS, showed independent associations with lower BI, but not AMT. These results highlight differences between various measures of anticholinergic drug exposure when studying their associations with functional status. PMID:25114784

  19. The effect of anticholinergic drugs on the electrolyte content of gastric juice

    PubMed Central

    Piper, D. W.; Stiel, Mirjam C.

    1961-01-01

    Gastric secretion was stimulated by insulin hypoglycaemia and the effect of increasing doses of anticholinergic drugs on the volume, acid, and electrolyte content of gastric juice was studied. The sodium and potassium output was depressed to a far less extent than the acid output and the drop in volume of secretion and acid output after anticholinergic drugs is almost entirely due to decreased acid secretion. With increasing anticholinergic suppression of the volume of secretion, there is a marked fall in potassium output and a lesser fall in sodium output. The potassium concentration showed a slight fall and there was a rise in sodium concentration. PMID:14486842

  20. Intranasal scopolamine preparation and method

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi (Inventor); Cintron, Nitza M. (Inventor)

    1991-01-01

    A new method and preparation for intranasal delivery of scopolamine provides a safe and effective treatment for motion sickness and other conditions requiring anticholinergic therapy. The preparation can be in the form of aqueous nasal drops, mist spray, gel or oinment. Intranasal delivery of scopolamine has similar bioavailability and effect of intravenous delivery and is far superior to oral dosage. Scopolamine is prepared in a buffered saline solution at the desired dosage rate for effective anticholinergic response.

  1. Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis.

    PubMed

    Madhuvrata, Priya; Singh, Manju; Hasafa, Zaid; Abdel-Fattah, Mohamed

    2012-11-01

    There is a lack of evidence about the efficacy and safety of anticholinergic drugs and about the optimal anticholinergic drug, if any, for the treatment of adult neurogenic detrusor overactivity (NDO). Review the current evidence on the efficacy, safety, and tolerability of anticholinergic drugs in the treatment of adult NDO. A literature search was conducted from 1966 to May 2011. Meta-analysis of all published randomised controlled trials (RCTs) comparing anticholinergic drugs with placebo and comparing different types, doses, and routes of administration of anticholinergic drugs, in adults with NDO, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The primary outcome was patient-reported cure/improvement of overactive bladder symptoms. Secondary outcomes were quality of life (QoL) changes, bladder diary events, urodynamic outcomes, adverse events, and costs to health services. A total of 960 patients from 16 RCTs with mean follow-up of 3.8 wk were included. Anticholinergic drugs were associated with statistically significantly better patient-reported cure/improvement (risk ratio: 2.80; 95% confidence interval [CI], 1.64 to 4.77), higher maximum cystometric capacity (weighted mean difference [WMD]: 49.49; 95% CI, 15.38 to 84.20), higher volume at first contraction (WMD: 49.92; 95% CI, 20.06 to 79.78), and lower maximum detrusor pressure (WMD: -38.30; 95% CI, -53.17 to -23.43) when compared with placebo. The dry-mouth rates were statistically significantly higher with anticholinergics, with no difference in withdrawals because of adverse events. There was no statistically significant difference in any of the outcomes between oxybutynin and other anticholinergics or among different doses and preparations of anticholinergic drugs. No study reported QoL changes or costs to health services. Compared with placebo, anticholinergic treatment in patients with NDO is associated with better patient

  2. Measuring anticholinergic drug exposure in older community-dwelling Australian men: a comparison of four different measures.

    PubMed

    Pont, Lisa G; Nielen, Johannes T H; McLachlan, Andrew J; Gnjidic, Danijela; Chan, Lewis; Cumming, Robert G; Taxis, Katja

    2015-11-01

    Anticholinergic drug exposure is associated with adverse outcomes in older people. While a number of tools have been developed to measure anticholinergic drug exposure, there is limited information about the agreement and overlap between the various scales. The aim of this study was to investigate the agreement and overlap between different measures of anticholinergic drug exposure in a cohort of community-dwelling older men. A cross-sectional study was used to compare anticholinergic drug exposure calculated using the Anticholinergic Risk Scale (ARS), the Anticholinergic Drug Scale (ADS), the Anticholinergic Cognitive Burden (ACB) and the Drug Burden Index anticholinergic subscale (DBI-ACH) in a cohort of community-dwelling men aged 70 years and older (n = 1696). Statistical agreement, expressed as Cohen's kappa (κ), between these measurements was calculated. Differences were found between the tools regarding the classification of anticholinergic drug exposure for individual participants. Thirteen percent of the population used a drug listed as anticholinergic on the ARS, 39% used a drug listed on the ADS and the ACB, and 18% of the population used one or more anticholinergic drugs listed on the DBI-ACH. While agreement was good between the ACB and ADS (κ = 0.628, 95% CI 0.593, 0.664), little agreement was found between remaining tools (κ = 0.091-0.264). With the exception of the ACB and ADS, there was poor agreement regarding anticholinergic drug exposure among the four tools compared in this study. Great care should be taken when interpreting anticholinergic drug exposure using existing scales due to the wide variability between the different scales. © 2015 The British Pharmacological Society.

  3. Anticonvulsant actions of anticholinergic drugs in soman poisoning. (Reannouncement with new availability information)

    SciTech Connect

    Capacio, B.R.; Shih, T.M.

    1991-12-31

    The acute effects of the organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds, aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman that produced 100% convulsions. Signs of intoxication as well as the time-to-onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 micro mol per kilogram for scopolamine HBr, biperiden, trihexyphenidy, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order by potency for inhibition of hypersecretions among these compounds was observed.

  4. Acetylcholine-Like Molecular Arrangement in Psychomimetic Anticholinergic Drugs

    PubMed Central

    Maayani, Saul; Weinstein, Harel; Cohen, Sasson; Sokolovsky, Mordechai

    1973-01-01

    A study of the relation between the psychotropic activity and the antagonism to acetylcholine observed for some heterocyclic amino esters and compounds of the phencyclidine series suggests some common molecular structural requirements for their properties. Criteria obtained from quantum mechanical calculations of acetylcholine-like molecules indicate that their molecular reactivity with the cholinergic receptor site follows a certain dynamic interaction pattern. This pattern suggests a certain molecular arrangement essential for the interaction, which is based on the electronic properties of the molecules and therefore remains valid for the evaluation of compounds which lack any apparent similarity to acetylcholine. This type of molecular arrangement is shown to be shared by both activators and inhibitors of the acetylcholine receptor discussed here, thus supporting the hypothesis of their binding to a common receptor. The differences in biological activity are attributed to the effect of molecular structural factors which are not commonly included in the molecular arrangement based on the active groups of acetylcholine. The role of such factors is revealed by a study of the observed differences in the cholinergic and psychomimetic activities of related pairs of isomers and enantiomers of the molecules investigated. Structural factors which interfere with the conformational changes occurring in the receptor protein induced by an activator are characterized through differences obtained by the comparative investigation of the activities of the agonist acetate and the antagonist benzilate amino esters of quinuclidine, tropine, and pseudotropine. The same factors are shown in studies of the phencyclidine series to contribute to the antagonism to acetylcholine activity that is closely related to the psychomimetic activity of these drugs in the central nervous system. Similarly, phencyclidine derivatives in which the characteristic acetylcholine-like molecular

  5. Acetylcholine-like molecular arrangement in psychomimetic anticholinergic drugs.

    PubMed

    Maayani, S; Weinstein, H; Cohen, S; Sokolovsky, M

    1973-11-01

    A study of the relation between the psychotropic activity and the antagonism to acetylcholine observed for some heterocyclic amino esters and compounds of the phencyclidine series suggests some common molecular structural requirements for their properties. Criteria obtained from quantum mechanical calculations of acetylcholine-like molecules indicate that their molecular reactivity with the cholinergic receptor site follows a certain dynamic interaction pattern. This pattern suggests a certain molecular arrangement essential for the interaction, which is based on the electronic properties of the molecules and therefore remains valid for the evaluation of compounds which lack any apparent similarity to acetylcholine. This type of molecular arrangement is shown to be shared by both activators and inhibitors of the acetylcholine receptor discussed here, thus supporting the hypothesis of their binding to a common receptor. The differences in biological activity are attributed to the effect of molecular structural factors which are not commonly included in the molecular arrangement based on the active groups of acetylcholine. The role of such factors is revealed by a study of the observed differences in the cholinergic and psychomimetic activities of related pairs of isomers and enantiomers of the molecules investigated. Structural factors which interfere with the conformational changes occurring in the receptor protein induced by an activator are characterized through differences obtained by the comparative investigation of the activities of the agonist acetate and the antagonist benzilate amino esters of quinuclidine, tropine, and pseudotropine. The same factors are shown in studies of the phencyclidine series to contribute to the antagonism to acetylcholine activity that is closely related to the psychomimetic activity of these drugs in the central nervous system. Similarly, phencyclidine derivatives in which the characteristic acetylcholine-like molecular

  6. Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents.

    PubMed

    Gjerden, Pål; Slørdal, Lars; Bramness, Jørgen G

    2009-12-01

    The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2-receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics.

  7. The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine

    PubMed Central

    Gjerden, Pål; Slørdal, Lars; Bramness, Jørgen G

    2009-01-01

    AIMS Extrapyramidal side-effects induced by antipsychotic drugs are treated with dose reduction or substitution with another antipsychotic drug or by the addition of anticholinergic antiparkinson agents. The withdrawal of orphenadrine from the Norwegian market provided a possibility to investigate to what degree these alternative measures were taken in clinical practice. METHODS Data were drawn from the Norwegian Prescription Database on the sales of antipsychotics and one of the two anticholinergic antiparkinson agents marketed in 2004, orphenadrine and biperiden, to a total of 39 758 outpatients. The patients were reinvestigated in 2007. The consequences of the withdrawal of orphenadrine from the Norwegian market in 2005 regarding dosing, switching and cessation of antipsychotics and use of anticholinergics were assessed for orphenadrine users compared with biperiden users. RESULTS Of the patients originally using orphenadrine, 28.4% stopped using the drug without reducing the antipsychotic dose or replacing orphenadrine with another anticholinergic agent. The corresponding number for biperiden users was 19.3%. Only 11.8% of patients switched to another antipsychotic drug, but they used significantly lower antipsychotic doses than those who stayed on the same drug. CONCLUSION The use of anticholinergic antiparkinson agents could be seen as superfluous for at least one-third of patients. PMID:19694744

  8. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review

    PubMed Central

    Herbison, Peter; Hay-Smith, Jean; Ellis, Gaye; Moore, Kate

    2003-01-01

    Objective To determine the effectiveness of anticholinergic drugs for the treatment of overactive bladder syndrome. Design Systematic review of randomised controlled trials. Data sources Published papers and abstracts. Study selection Randomised controlled trials with anticholinergic drug treatment in one arm and placebo in another. Data extraction Primary outcomes of interest were patient perceived cure or improvement in symptoms, differences in number of incontinent episodes and number of voids in 24 hours, and side effects. Secondary outcomes of interest were urodynamic measures of bladder function (volume at first contraction, maximum cystometric capacity, and residual volume) and adverse events. Data synthesis 32 trials were included, totalling 6800 participants. Most trials were described as double blind but were variable in other aspects of quality. At the end of treatment, cure or improvement (relative risk 1.41, 95% confidence interval 1.29 to 1.54), differences in incontinent episodes in 24 hours (estimated mean difference 0.6, 0.4 to 0.8), number of voids in 24 hours (0.6, 0.4 to 0.8), maximum cystometric capacity (54 ml, 43 ml to 66 ml), and volume at first contraction (52 ml, 37 ml to 67 ml), were significantly in favour of anticholinergics (P<0.0001 for all). Anticholinergics were associated with significantly higher residual volumes (4 ml, 1 ml to 7 ml; P=0.02) and an increased rate of dry mouth (relative risk 2.56, 2.24 to 2.92; P<0.0001). Sensitivity analysis, although affected by small numbers of studies, showed little likelihood of an effect of age, sex, diagnosis, or choice of drug. Conclusions Although statistically significant, the differences between anticholinergic drugs and placebo were small, apart from the increased rate of dry mouth in patients receiving active treatment. For many of the outcomes studied, the observed difference between anticholinergics and placebo may be of questionable clinical significance. None of these studies

  9. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study

    PubMed Central

    Carrière, Isabelle; Fourrier-Reglat, Annie; Dartigues, Jean-François; Rouaud, Olivier; Pasquier, Florence; Ritchie, Karen; Ancelin, Marie-Laure

    2009-01-01

    Objective To examine the association between use of medications with anticholinergic properties, cognitive decline and incident dementia in a large community-based sample of subjects aged 65 years and over. Methods Participants were 4128 women and 2784 men from a population-based cohort recruited from three French cities. Cognitive performance, clinical diagnosis of dementia and anticholinergic use were evaluated at base-line, 2 and 4 year later. Results 7.5% of subjects reported anticholinergic drug use at base-line. Multivariate adjusted logistic regression indicated that women reporting anticholinergic drugs at base-line showed greater decline over four years in verbal fluency scores (OR=1.41, CI=1.11–1.79) and in global cognitive functioning (OR=1.22, CI=0.96–1.55) than women not using anticholinergic drugs. In men, an association was found with decline in visual memory (OR=1.63, CI=1.08–2.47) and to a lesser extent in executive function (OR=1.47, CI=0.89–2.44). Significant interactions were observed in women between anticholinergic use and age, apolipoprotein E, or hormone replacement therapy. A significantly 1.4–2 fold higher risk of cognitive decline was observed for continuous anticholinergic users but not for those having discontinued. The risk of incident dementia over the four-year followup was also increased in continuous users (HR=1.65, CI=1.00–2.73) but not in those having discontinued anticholinergic drugs (HR=1.28, CI=0.59–2.76). Conclusions Elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatment was associated with a decreased risk. Physicians should carefully consider prescription of anticholinergic drugs in elderly people especially in the oldest old and persons at high genetic risk of cognitive disorder. PMID:19636034

  10. [Impact on cognitive function of anticholinergic drugs used for the treatment of overactive bladder in the elderly].

    PubMed

    Kerdraon, J; Robain, G; Jeandel, C; Mongiat Artus, P; Gamé, X; Fatton, B; Scheiber-Nogueira, M C; Vetel, J-M; Mares, P; Petit, A-C; Amarenco, G

    2014-09-01

    Describe the central nervous system (CNS) adverse effects of anticholinergic drugs used for the treatment of overactive bladder (OAB) in the elderly. Relevant data from the literature were identified primarily through a Medline search of articles published through December 2013. The search terms included overactive bladder, central nervous system, elderly, anticholinergic, and antimuscarinic. Articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly. Several anticholinergic drugs are available for the treatment of OAB, including oxybutinin, tolterodine, trospium chloride, solifenacine, fesoterodine. Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutinin, lower for tolterodine, solifenacine, and darifenacine, and lowest for fesoterodine and trospium chloride. Unwanted CNS adverse effects depend in part on patient specific variability in pharmacokinetic parameters, blood-brain barrier permeability, degree of cholinergic neuronal degeneration, total anticholinergic drug burden and patient's baseline cognitive status. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and coma. Among the different anticholinergic agents, oxybutinin has been associated with cognitive impairment and trospium chloride and fesoterodine have shown favorable CNS tolerability. Anticholinergic drugs improve significatively overactive bladder symptoms in older adults. However, potential CNS adverse effects of anticholinergic agents used in OAB must lead to a full evaluation before and during the treatment in order to evaluate benefice, risks and central side effects in this frail population. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Anticholinergic drugs versus non-drug active therapies for non-neurogenic overactive bladder syndrome in adults.

    PubMed

    Rai, Bhavan Prasad; Cody, June D; Alhasso, Ammar; Stewart, Laurence

    2012-12-12

    Overactive bladder syndrome is defined as urgency with or without urgency incontinence, usually with frequency and nocturia. Pharmacotherapy with anticholinergic drugs is often the first line medical therapy, either alone or as an adjunct to various non-pharmacological therapies after conservative options such as reducing intake of caffeine drinks have been tried. Non-pharmacologic therapies consist of bladder training, pelvic floor muscle training with or without biofeedback, behavioural modification, electrical stimulation and surgical interventions. To compare the effects of anticholinergic drugs with various non-pharmacologic therapies for non-neurogenic overactive bladder syndrome in adults. We searched the Cochrane Incontinence Group Specialised Register (searched 4 September 2012), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, and the reference lists of relevant articles. All randomised or quasi-randomised, controlled trials of treatment with anticholinergic drugs for overactive bladder syndrome or urgency urinary incontinence in adults in which at least one management arm involved a non-drug therapy. Trials amongst patients with neurogenic bladder dysfunction were excluded. Two authors evaluated the trials for appropriateness for inclusion and risk of bias. Two authors were involved in the data extraction. Data extraction was based on predetermined criteria. Data analysis was based on standard statistical approaches used in Cochrane reviews. Twenty three trials were included with a total of 3685 participants, one was a cross-over trial and the other 22 were parallel group trials. The duration of follow up varied from two to 52 weeks. The trials were generally small and of poor methodological quality. During treatment, symptomatic improvement was more common amongst those participants on anticholinergic drugs compared with bladder training in seven small trials (73/174, 42% versus 98/172, 57% not

  12. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID Study

    PubMed Central

    Lechevallier-Michel, Nathalie; Molimard, Mathieu; Dartigues, Jean-François; Fabrigoule, Colette; Fourrier-Réglat, Annie

    2005-01-01

    Objectives To measure the association between the use of drugs with anticholinergic properties and cognitive performance in an elderly population, the PAQUID cohort. Methods The sample studied was composed of 1780 subjects aged 70 and older, living at home in South western France. Data on socio-demographic characteristics, medical history and drug use were collected using a standardized questionnaire. Cognitive performance was assessed using the following neuropsychological tests: the Mini-Mental State Examination (MMSE) which evaluates global cognitive functioning, the Benton Visual Retention Test (BVRT) which assesses immediate visual memory, and the Isaacs’ Set Test (IST) which assesses verbal fluency. For each test, scores were dichotomized between low performance and normal to high performance using the score at the 10th percentile of the study sample as the cut-off point, according to age, gender and educational level. The association between the use of drugs with anticholinergic properties and cognitive performance was examined using logistic regression models, adjusting for several potential confounding factors. Results About 13.7% of the subjects used at least one drug with anticholinergic properties. In multivariate analyses, the use of these drugs was significantly associated with low performance in the BVRT [odds ratio (OR) = 1.6; 95% confidence interval (CI) 1.1, 2.3] and in the IST (OR = 1.9; 95% CI 1.3, 2.8). The association found with low performance in the MMSE (OR = 1.4; 95% CI 1.0, 2.1) was barely statistically significant. Conclusion These findings suggest that the use of drugs with anticholinergic properties is associated with low cognitive performance among community-dwelling elderly people. PMID:15676035

  13. Anticholinergic behavioral effect of phencyclidine.

    PubMed

    Glick, S D; Cox, R D; Maayani, S; Meibach, R D

    1979-10-26

    Phencyclidine (PCP) impaired spatial alternation performance in rats. This effects was mimicked by antimuscarinic anticholinergics (scopolamine, atropine) and PCP derivatives (ketamine, cyclohexamine) but not by a variety of other agents. Muscarinic cholinergic agonists antagonized PCP. Impairment of spatial alteration performance by PCP appears to be mediated, at least in part, by and anticholinergic action; this is the first instance of a behavioral effect of PCP that can be largely attributed to a specific mechanism.

  14. Changes in extrapyramidal symptoms following anticholinergic drug withdrawal.

    PubMed

    Perenyi, A; Gardos, G; Samu, I; Kallos, M; Cole, J O

    1983-03-01

    An antiparkinson drug (APK) withdrawal study was carried out in 34 schizophrenic outpatients on maintenance neuroleptics. Sixty-five percent of patients were without major complaints after 2 weeks of APK discontinuation, while 35% reported adverse effects including extrapyramidal, autonomic, and behavioral symptoms. Male patients and those on higher diethazine doses before withdrawal reported more complaints. Ratings showed significant increases of parkinsonism, as well as dyskinesia following APK withdrawal. No clinical evidence was obtained in support of the notion of cholinergic hypersensitivity in patients showing "tremors" at baseline.

  15. Scopolamine induced amnesia is reversed by Bacopa monniera through participation of kinase-CREB pathway.

    PubMed

    Saraf, Manish Kumar; Anand, Akshay; Prabhakar, Sudesh

    2010-02-01

    Scopolamine, an anticholinergic drug, is reported to produce amnesia by interference of long term potentiation and has been used for discerning the efficacy of various antiamnesic drugs. The intoxication with anticholinergics and benzodiazepines tend to produce neurodegeneration which cause memory deficits. Our earlier reports have shown the antiamnesic drug, B. monniera to be capable of alleviating diazepam induced memory deficits. We have now tested how scopolamine affects downstream signaling molecules of long term potentiation and if B. monniera can also modulate the scopolamine induced amnesia. We used Morris water maze scale to test the amnesic effect of scopolamine and its reversal by B. monniera. Rota-rod test was used to screen muscle coordination activity of mice before water maze investigations were carried out. The results showed that scopolamine downregulated protein kinase C and iNOS without affecting cAMP, protein kinase A, calmodulin, MAP kinase, nitrite, CREB and pCREB. B. monniera reversed the scopolamine induced amnesia by significantly improving calmodulin and by partially attenuating protein kinase C and pCREB. These observations suggest involvement of calmodulin in evoking antiamnesic effects of B. monniera.

  16. Methyllycaconitine- and scopolamine-induced cognitive dysfunction: differential reversal effect by cognition-enhancing drugs

    PubMed Central

    Andriambeloson, Emile; Huyard, Bertrand; Poiraud, Etienne; Wagner, Stéphanie

    2014-01-01

    There is a growing body of evidence pointing to the pivotal role of alpha-7 nicotinic acetylcholine receptor (α7 nAchR) dysfunction in cognitive disorders such as Alzheimer’s disease or schizophrenia. This study was undertaken to establish and characterize an in vivo model for cognitive disorder secondary to the blockade of α7 nAChR by its specific antagonist, methyllycaconitine (MLA). The results show that MLA elicited cognitive dysfunction as assessed by reduced spontaneous alternation of mice in the T-maze. The maximal effect of MLA produced 25–30% reduction in the spontaneous alternation of mice, a level comparable with that induced by the muscarinic antagonism of scopolamine. Donepezil and galantamine fully reversed both MLA and scopolamine-induced cognitive dysfunction. However, the ED50 of donepezil and galantamine was significantly shifted to the left in the MLA- compared to scopolamine-treated mice (0.0005 and 0.002 mg/kg for donepezil; 0.0003 and 0.7 mg/kg for galantamine). Moreover, memantine elicited marked reversion of cognitive dysfunction (up to 70%) in MLA-treated mice while only a weak reversal effect at high dose of memantine (less than 20%) was observed in scopolamine-treated mice. The above findings indicate that MLA-induced cognitive dysfunction in the mouse is highly sensitive and more responsive to the current procognitive drugs than the traditional scopolamine-based assay. Thus, it can be of value for the preclinical screening and profiling of cognition-enhancing drugs. PMID:25505596

  17. Structural changes and inhibition of sucrase after binding of scopolamine.

    PubMed

    Minai-Tehrani, Dariush; Fooladi, Negar; Minoui, Saeed; Sobhani-Damavandifar, Zahra; Aavani, Tooka; Heydarzadeh, Soraya; Attar, Farnoosh; Ghaffari, Mina; Nazem, Habibollah

    2010-06-10

    Scopolamine (hyoscine) is commonly used as an anticholinergic drug to relieve nausea, vomiting and dizziness of a motion sickness as well as recovery from anesthesia and surgery. Sucrase as a hydrolytic enzyme breaks down sucrose into its monomers, glucose and fructose. The aim of this study was to evaluate the effect of scopolamine on the activity and the structural changes of yeast sucrase. The results showed that binding of scopolamine to sucrase could inhibit the enzyme activity. A non-competitive inhibition was observed in different concentrations of scopolamine (0.6 to 3.6mM). The study by circular dichroism measurement in far-UV showed that the absolute enzyme exhibited a flat negative trough, indicating the presence of alpha-helices and beta-sheet structures in the enzyme. Binding of the inhibitor on the enzyme made a deeper trough at 218nm, suggesting the increasing of beta-sheet content of the enzyme. Fluorescence measurement showed that binding of scopolamine to free enzyme and enzyme-substrate complex increased the peak intensity at 350nm and also induced red shift. Our findings suggest that scopolamine binds to the location other than the active site of enzyme and that the binding causes structural changes and inhibits the enzyme activity.

  18. A Predictive In Vitro Model of the Impact of Drugs with Anticholinergic Properties on Human Neuronal and Astrocytic Systems

    PubMed Central

    Woehrling, Elizabeth K.; Parri, H. Rheinallt; Tse, Erin H. Y.; Hill, Eric J.; Maidment, Ian D.; Fox, G. Christopher; Coleman, Michael D.

    2015-01-01

    The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly. PMID:25738989

  19. Abuse of the over-the-counter antispasmodic butylscopolamine for the home synthesis of psychoactive scopolamine.

    PubMed

    Kummer, Sebastian; Rickert, Annette; Daldrup, Thomas; Mayatepek, Ertan

    2016-07-01

    We report on two patients who ingested psychoactive scopolamine that was synthesized at home from butylscopolamine (Buscopan®), which is available as over-the-counter antispasmodic in nearly 100 countries worldwide. Patient 1 presented with severe central anticholinergic toxidrome, while patient 2 suffered from minor symptoms. An empty blister of Buscopan® was found in the patients' home, but initially was not suspected to be causative for the observed central anticholinergic symptoms, as Buscopan® is not able to pass the blood-brain barrier in its native form. Only later, the information by third parties and a Google search helped to identify homemade scopolamine derived from Buscopan® as the responsible agent in these two cases. Retrospectively, scopolamine could be detected in serum and urine of both patients, while it was absent in one control after ingestion of native Buscopan®. Over-the-counter drugs can be used to synthesize psychoactives with means that are available in every household. Such knowledge can spread via social media and internet discussion boards long before appearing in medical literature. While typical clinical presentation often enables clinicians to adequately identify and treat specific toxidromes, these sources of information need to be increasingly taken into account by medical professionals for identification of its causative agent. This potential of Buscopan® might gain importance as an easily accessible source of psychoactive scopolamine. • Substances with central anticholinergic effects are known for their hallucinogenic potential and may be used as psychoactives. What is New: • The over-the-counter antispasmodic butylscopolamine (Buscopan®) can be abused to synthesize anticholinergic, psychoactive scopolamine at home with means that are available in every household.

  20. Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats.

    PubMed

    Ishizaki, J; Yokogawa, K; Nakashima, E; Ohkuma, S; Ichimura, F

    1998-07-01

    Ammonium chloride (NH4Cl) increases lysosomal pH and thereby abolishes intralysosomal accumulation of drugs. Its effect on the tissue distribution of biperiden and trihexyphenidyl in rats has been investigated. The tissue-plasma concentration ratios (Kp) of these drugs in various tissues were determined by infusion studies at steady-state in the presence or absence of NH4Cl. Treatment with NH4Cl reduced the Kp values for both drugs, causing the largest reduction in Kp in the lung (52.1 to 11.8 for biperiden and 59.5 to 18.9 for trihexyphenidyl; ratios of decrease 0.77 and 0.68, respectively), followed by the heart and kidneys, with relatively small reductions in the brain, gut, muscle and fat. Subcellular fractionation studies in the lung indicated that the subcellular fraction-plasma concentration ratio of each drug at the steady state (K(p,sf)) was reduced by treatment with NH4Cl, with the largest decrease in the post-nuclear fraction (ratio of decrease 0.82 for biperiden and 0.74 for trihexyphenidyl), followed by the nucleus, microsomes and supernatant, in that order. A strong correlation was found between the ratio of decrease in K(p,sf) after NH4Cl treatment and the specific activity of acid phosphatases, a marker of lysosomes, in each fraction (biperiden, r = 0.948; trihexyphenidyl, r = 0.945). These results suggest that acidic organelles contribute significantly to the distribution kinetics of anticholinergic drugs.

  1. Effects of injectable anticholinergic drugs on soman-induced lethality and convulsant/subconvulsant activity

    SciTech Connect

    Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Bowersox, S.L.; Anders, J.C.

    1993-05-13

    FDA approved, injectable preparations of candidate compounds BENZTROPINE (BZT), 1.0 mg/ml; biperiden (BIP), 5.0 mg/ml; dicyclomine (DCL), 10 mg/ml; 1-hyoscyamine (HYO), 0.5 mg/ml; orphenadrine (ORP), 30 mg/ml; scopolamine (SCP), 1.0 mg/ml were tested in parallel with diazepam (DZ, the standard) in male guinea pigs against ongoing soman induced convulsive (CV)/sub-CV activity. Three trained graders concurrently assigned CV/sub-CV scores (12 - convulsions; 0 normal) to each animal. Animals received (im) pyridostigmine (PYR; 26 ug/kg) 30 min before soman (56 ug/kg; 2 LD50), atropine (2 mg/kg) admixed with 2-PAM (25 mg/kg) at one min after soman, and the candidate drug preparation at 5.67 min post soman, a time when CV activity is assured. BIP and SCP demonstrated efficacy over dosage ranges between 10 and 0.3 and 1.0 and 0.13 mg/kg, respectively, while the other preparations were less effective at their respective maximum dosages. At optimal dosages of SCP (0.5 mg/kg) and BIP (10 mg/kg), the CV/sub-CV scores were significantly lower (p < 0.05) than those of DZ.

  2. Use of Physostigmine by the Intravenous, Intramuscular, and Oral Routes in the Therapy of Anticholinergic Drug Intoxication

    DTIC Science & Technology

    1976-05-01

    large doses of other compounds, such as phenothiazine8 and certain tricyclic antidepressants , 9 •1 1 which appear to have some degree of cholinergic... time , physostigmine was available commercially in a preparation containing 4 mg/ml* and this dose represented a volume of about I ml for a 70-kg man...After a light breakfast, they received an anticholinergic drug (intravenously or intramuscularly) and, at the time (s) specified under results, were

  3. Scopolamine-induced convulsions in fasted mice after food intake: effects of glucose intake, antimuscarinic activity and anticonvulsant drugs.

    PubMed

    Enginar, Nurhan; Nurten, Asiye; Celik, Pinar Yamantürk; Açikmeşe, Bariş

    2005-09-01

    The present study was performed to further evaluate the contribution of antimuscarinic activity and hypoglycaemia to the development of scopolamine-induced convulsions in fasted mice after food intake. The effects of anticonvulsant drugs on convulsions were also evaluated. Antimuscarinic drugs atropine (3 mg/kg) and biperiden (10 mg/kg) were given intraperitoneally (i.p) to animals fasted for 48 h. Like scopolamine, both drugs induced convulsions after animals were allowed to eat ad libitum. Another group of animals was given glucose (5%) in drinking water during fasting. These animals, although they had normoglycaemic blood levels after fasting, also developed convulsions after treated with scopolamine i.p. (3 mg/kg), atropine (3 mg/kg) or biperiden (10 mg/kg) and allowed to eat ad libitum. Among the drugs studied, only valproate (340 mg/kg), gabapentin (50 mg/kg) and diazepam (2.5 and 5 mg/kg) markedly reduced the incidence of scopolamine-induced convulsions. The present results indicate that antimuscarinic activity, but not hypoglycaemia, underlies these convulsions which do not respond to most of the conventional anticonvulsant drugs.

  4. Short-term and long-term effects of diazepam on the memory for discrimination and generalization of scopolamine.

    PubMed

    Casasola-Castro, C; Weissmann-Sánchez, L; Calixto-González, E; Aguayo-Del Castillo, A; Velázquez-Martínez, D N

    2017-07-22

    Benzodiazepines are among the most widely prescribed and misused psychopharmaceutical drugs. Although they are well-tolerated, they are also capable of producing amnestic effects similar to those observed after pharmacological or organic cholinergic dysfunction. To date, the effect of benzodiazepine diazepam on the memory for discrimination of anticholinergic drugs has not been reported. The aim of the present study was to analyze the immediate and long-term effects of diazepam on a drug discrimination task with scopolamine. Male Wistar rats were trained to discriminate between scopolamine and saline administration using a two-lever discrimination task. Once discrimination was acquired, the subjects were divided into three independent groups, (1) control, (2) diazepam, and (3) diazepam chronic administration (10 days). Subsequently, generalization curves for scopolamine were obtained. Additionally, the diazepam and control groups were revaluated after 90 days without having been given any other treatment. The results showed that diazepam produced a significant reduction in the generalization gradient for scopolamine, indicating an impairment of discrimination. The negative effect of diazepam persisted even 90 days after drug had been administered. Meanwhile, the previous administration of diazepam for 10 days totally abated the generalization curve and the general performance of the subjects. The results suggest that diazepam affects memory for the stimulus discrimination of anticholinergic drugs and does so persistently, which could be an important consideration during the treatment of amnesic patients with benzodiazepines.

  5. Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics.

    PubMed

    McBride, W G; Hicks, L J

    1987-01-01

    It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Cesarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals. Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 micrograms/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta. The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Postoperative Anticholinergic Poisoning: Concealed Complications of a Commonly Used Medication.

    PubMed

    Zhang, Xiao Chi; Farrell, Natalija; Haronian, Thomas; Hack, Jason

    2017-07-27

    Scopolamine is a potent anticholinergic compound used commonly for the prevention of postoperative nausea and vomiting. Scopolamine can cause atypical anticholinergic syndromes due to its prominent central antimuscarinic effects. A 47-year-old female presented to the emergency department (ED) 20 h after hospital discharge for a right-knee meniscectomy, with altered mental status (AMS) and dystonic extremity movements that began 12 h after her procedure. Her vital signs were normal and physical examination revealed mydriasis, visual hallucinations, hyperreflexia, and dystonic movements. Laboratory data, lumbar puncture, and computed tomography were unrevealing. The sustained AMS prompted a re-evaluation that revealed urinary overflow with 500 mL of retained urine discovered on ultrasound and a scopolamine patch hidden behind her ear. Her mental status improved shortly after patch removal and physostigmine, with complete resolution after 24 h with discharge diagnosis of scopolamine-induced anticholinergic toxicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although therapeutically dosed scopolamine transdermal patches rarely cause complications, incomplete toxidromes can be insidiously common in polypharmacy settings. Providers should thoroughly evaluate the skin of intoxicated patients for additional adherent medications that may result in a delay in ED diagnosis and curative therapies. Our case, as well as rare case reports of therapeutic scopolamine-induced anticholinergic toxicity, demonstrates that peripheral anticholinergic effects, such as tachycardia, dry mucous membranes, and hyperpyrexia are often not present, and incremental doses of physostigmine may be required to reverse scopolamine's long duration of action. This further complicates identification of the anticholinergic toxidrome and diagnosis. Published by Elsevier Inc.

  7. Delirium due to scopolamine patch in a 4-year-old boy.

    PubMed

    Lin, Yang-Guang; Chen, Po-Hon; Chang, Fang-Yuan; Wu, Li-Te; Liao, Kuo-Yu; Wu, Tzee-Chung

    2011-03-01

    The scopolamine patch is usually used to reduce postoperative nausea and vomiting associated with anesthesia and/or surgery. It is also commonly used for the prevention of motion sickness. Transdermal scopolamine patches have been used for decades and there are few reports in the literature of toxic psychosis associated with the product. Most documented cases of acute psychosis following administration of scopolamine or other anticholinergic agents have been from the adult population. Here we present a 4-year-old boy with deteriorated cognitive function and changed mental status acutely. Besides flushing skin and psychotic behaviors including bizarre actions, hallucinations, aggressive behavior, hyperactivity, and incoherent speech were also noticed. Symptoms and signs were resolved after removal of scopolamine patch and conservative management. This case is possibly one of the youngest patients to exhibit such toxic effects. We hope to relay information about common agents with anticholinergic effects to clinical practitioners and remind that drug-induced psychosis should be considered in children with acute changes in behavior.

  8. Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial.

    PubMed

    Pitkala, Kaisu H; Juola, Anna-Liisa; Soini, Helena; Laakkonen, Marja-Liisa; Kautiainen, Hannu; Teramura-Gronblad, Mariko; Finne-Soveri, Harriet; Bjorkman, Mikko

    2012-06-18

    Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people's drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents' quality of life and use of health services. During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months. The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations. To our knowledge, this is the first large

  9. Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people’s drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents’ quality of life and use of health services. Methods and design During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months. The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations. Discussion To our

  10. Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice

    PubMed Central

    Saraf, Manish Kumar; Prabhakar, Sudesh; Khanduja, Krishan Lal; Anand, Akshay

    2011-01-01

    Scopolamine, an anticholinergic, is an attractive amnesic agent for discerning the action of candidate antiamnesic drugs. Bacopa monniera Linn (Syn. Brahmi) is one such antiamnesic agent that is frequently used in the ancient Indian medical system. We have earlier reported the reversal of diazepam-induced amnesia with B. monniera. In this study we wanted to test if scopolamine-induced impairment of spatial memory can also be ameliorated by B. monniera using water maze mouse model. The objective of study was to study the effect of B. monniera on scopolamine-induced amnesia. We employed Morris water maze scale to test the amnesic effect of scopolamine and its reversal by B. monniera. Rotarod test was conducted to screen muscle coordination activity of mice. Scopolamine significantly impaired the acquisition and retrieval of memory producing both anterograde and retrograde amnesia. Bacopa monniera extract was able to reverse both anterograde and retrograde amnesia. We propose that B. monniera's effects on cholinergic system may be helpful for developing alternative therapeutic approaches for the treatment of Alzheimer's disease. PMID:21607013

  11. Development of a screening method for the most commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine and biperiden.

    PubMed

    Hadidi, Kamal A

    2004-10-01

    A sensitive and rapid method for the simultaneous determination of three commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine, and biperiden in plasma and urine has been developed using solid phase extraction and GC-MS. Linearity was established from therapeutic to fatal concentrations of the three drugs; 5-300 ng/ml in plasma, with correlation coefficient r(2) > or = 0.9978 and 10-800 ng/ml in urine r(2) > or = 0.9993. Recoveries were in the range of 86-92% and intra-day and inter-day relative standard deviations (n = 6) were in the range of 6.6-10.3% for the three drugs at three different concentrations in plasma and urine. The base peak m/z 98 for trihexyphenidyl, m/z 84 for procyclidine, and m/z 98 and 218 for biperiden, and m/z 339 for papaverine (internal standard) were monitored at selective ion monitoring; their retention times were 8.10, 8.67 and 8.92 min, respectively, and 14.79 min for the internal standard with analysis time of 16.75 min. The limit of detection of 0.5 ng/ml was attained for trihexyphenidyl and procyclidine, while for biperiden 2.0 and 1.0 ng/ml in spiked plasma and urine, respectively. This method has been applied to forensic and authentic samples taken from abuser and patients using these drugs. The method will offer the clinicians and the legal authority the right diagnosis regarding the anticholinergic involved in any case of abuse with less than 1 h per sample (plasma or urine) from the time of receiving.

  12. Amnestic drugs in the odor span task: Effects of flunitrazepam, zolpidem and scopolamine.

    PubMed

    Galizio, Mark; Mathews, Michael; Mason, Madeleine; Panoz-Brown, Danielle; Prichard, Ashley; Soto, Paul

    2017-09-08

    The odor span task is an incrementing non-matching-to-sample procedure designed to provide an analysis of working memory capacity in rodents. The procedure takes place in an arena apparatus and rats are exposed to a series of odor stimuli in the form of scented lids with the selection of new stimuli reinforced. This procedure makes it possible to study drug effects as a function of the number of stimuli to remember. In the present study, the non-selective positive allosteric GABAA receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination. In contrast, the alpha-1 selective positive GABAA receptor modulator zolpidem and the cholinergic receptor antagonist scopolamine only impaired odor span at doses that produced more global impairment, including decreased accuracy in the control discrimination and increased response omissions in the both the odor span and control discrimination procedures. Even though the effects of flunitrazepam were selective to odor span performance, they did not depend on the number of stimuli to remember-the same degree of impairment occurred regardless of the memory load. These findings suggest that flunitrazepam interfered selectively with conditional discrimination performance rather than working memory and tentatively suggest that flunitrazepam's selective effects in the odor span task relative to the control odor discrimination are mediated by one or more non-alpha1 GABAA receptor subtypes. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Learning and memory in the forced swimming test: effects of antidepressants having varying degrees of anticholinergic activity.

    PubMed

    Enginar, Nurhan; Yamantürk-Çelik, Pınar; Nurten, Asiye; Güney, Dilvin Berrak

    2016-07-01

    The antidepressant-induced reduction in immobility time in the forced swimming test may depend on memory impairment due to the drug's anticholinergic efficacy. Therefore, the present study evaluated learning and memory of the immobility response in rats after the pretest and test administrations of antidepressants having potent, comparatively lower, and no anticholinergic activities. Immobility was measured in the test session performed 24 h after the pretest session. Scopolamine and MK-801, which are agents that have memory impairing effects, were used as reference drugs for a better evaluation of the memory processes in the test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased immobility time suggesting impaired "learning to be immobile" in the animals. The test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg), moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg) decreased immobility time, which suggested that the drugs exerted antidepressant activity or the animals did not recall that attempting to escape was futile. The test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg) produced no effect on immobility time. Even though the false-negative and positive responses made it somewhat difficult to interpret the findings, this study demonstrated that when given before the pretest antidepressants with or without anticholinergic activity seemed to be devoid of impairing the learning process in the test.

  14. Amnesic effects of the anticholinergic drugs, trihexyphenidyl and biperiden: differences in binding properties to the brain muscarinic receptor.

    PubMed

    Kimura, Y; Ohue, M; Kitaura, T; Kihira, K

    1999-07-10

    An amnesic effect of anticholinergic drugs was previously described from several behavioral studies. We examined this effect induced by trihexyphenidyl and biperiden, clinically used in the parkinsonism and schizophrenic patients, by using passive avoidance tasks. Both of these drugs (0.1-10 mg/kg, s.c.) showed dose-dependent amnesic effects in the acquisition and retrieval phases. However, the effect induced by trihexyphenidyl was transient, whereas that of biperiden was long-lasting. To clarify the reason for the different duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [(3)H]quinuclidinyl benzilate ([(3)H]QNB) on the muscarinic receptor (showed increased K(d) and unchanged B(max) value), while biperiden decreased [(3)H]QNB binding (B(max) value) significantly. Furthermore, in an exchange assay for receptor inactivation, trihexyphenidyl binding to muscarinic receptors was exchanged by [(3)H]QNB completely, but biperiden decreased the exchangeable binding of [(3)H]QNB in a dose dependent manner (0.1-100 nM). These results suggested that the binding of trihexyphenidyl and biperiden to muscarinic receptor might be completely reversible and partially irreversible, respectively, whereas the K(i) values of these two drugs were similar. In conclusion, this difference in binding property may explain the difference in the time-course of the amnesic effect induced by trihexyphenidyl and biperiden.

  15. Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. Cross sectional data from 21 Norwegian nursing homes

    PubMed Central

    Kersten, Hege; Molden, Espen; Willumsen, Tiril; Engedal, Knut; Wyller, Torgeir Bruun

    2013-01-01

    Aim This study evaluated a presumed gradual decline in cognitive function in nursing home residents when the anticholinergic drug scale (ADS) score increased above 3. Method The study population was recruited from 21 nursing homes in Norway. Criteria for inclusion were ADS score ≥ 3 and no severe dementia, defined as Clinical Dementia Rating (CDR) score < 3. Primary cognitive end points were CERAD 10‐word lists for recall and Mini Mental State Examination (MMSE). Secondary end points were activity of daily living (ADL), mouth dryness and serum anticholinergic activity (SAA). The patients were stratified into subgroups according to ADS score, i.e. a reference group with score 3 and test groups with scores 4, 5 or ≥6. End points were compared by analyses of covariance (ancova). Results Overall, 230 of the 1101 screened nursing home residents (21%) had an ADS score ≥3. After exclusion 101 residents were recruited and among these, 87 managed to participate in the study. No significant differences were detected in cognitive function or ADL when ADS increased above 3 (P > 0.10), but in vivo (mouth dryness) and in vitro (SAA) measures of peripheral anticholinergic activity were significantly higher in patients with an ADS score ≥6 (P < 0.01). Conclusion The present study does not support a progressive decline in cognitive function with ADS score above 3. This might indicate that the ADS score model has limited potential to predict the clinical risk of central anticholinergic side effects in frail elderly patients receiving multiple anticholinergic drugs. PMID:22924454

  16. Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. Cross sectional data from 21 Norwegian nursing homes.

    PubMed

    Kersten, Hege; Molden, Espen; Willumsen, Tiril; Engedal, Knut; Bruun Wyller, Torgeir

    2013-03-01

    This study evaluated a presumed gradual decline in cognitive function in nursing home residents when the anticholinergic drug scale (ADS) score increased above 3. The study population was recruited from 21 nursing homes in Norway. Criteria for inclusion were ADS score ≥ 3 and no severe dementia, defined as Clinical Dementia Rating (CDR) score < 3. Primary cognitive end points were CERAD 10-word lists for recall and Mini Mental State Examination (MMSE). Secondary end points were activity of daily living (ADL), mouth dryness and serum anticholinergic activity (SAA). The patients were stratified into subgroups according to ADS score, i.e. a reference group with score 3 and test groups with scores 4, 5 or ≥6. End points were compared by analyses of covariance (ancova). Overall, 230 of the 1101 screened nursing home residents (21%) had an ADS score ≥3. After exclusion 101 residents were recruited and among these, 87 managed to participate in the study. No significant differences were detected in cognitive function or ADL when ADS increased above 3 (P > 0.10), but in vivo (mouth dryness) and in vitro (SAA) measures of peripheral anticholinergic activity were significantly higher in patients with an ADS score ≥6 (P < 0.01). The present study does not support a progressive decline in cognitive function with ADS score above 3. This might indicate that the ADS score model has limited potential to predict the clinical risk of central anticholinergic side effects in frail elderly patients receiving multiple anticholinergic drugs. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  17. Neuromodulatory propensity of Bacopa monniera against scopolamine-induced cytotoxicity in PC12 cells via down-regulation of AChE and up-regulation of BDNF and muscarnic-1 receptor expression.

    PubMed

    Pandareesh, M D; Anand, T

    2013-10-01

    Scopolamine is a competitive antagonist of muscarinic acetylcholine receptors, and thus classified as an anti-muscarinic and anti-cholinergic drug. PC12 cell lines possess muscarinic receptors and mimic the neuronal cells. These cells were treated with different concentrations of scopolamine for 24 h and were protected from the cellular damage by pretreatment with Bacopa monniera extract (BME). In current study, we have explored the molecular mechanism of neuromodulatory and antioxidant propensity of (BME) to attenuate scopolamine-induced cytotoxicity using PC12 cells. Our results elucidate that pretreatment of PC12 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by 3 μg/ml scopolamine to 54.83 and 30.30 % as evidenced by MTT and lactate dehydrogenase assays respectively. BME (100 μg/ml) ameliorated scopolamine effect by down-regulating acetylcholine esterase and up-regulating brain-derived neurotropic factor and muscarinic muscarinic-1 receptor expression. BME pretreated cells also showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant enzymes and lipid peroxidation. This result indicates that the scopolamine-induced cytotoxicity and neuromodulatory changes were restored with the pretreatment of BME.

  18. Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: A systematic review and meta-analysis

    PubMed Central

    Ruxton, Kimberley; Woodman, Richard J; Mangoni, Arduino A

    2015-01-01

    Aim The aim was to investigate associations between drugs with anticholinergic effects (DACEs) and cognitive impairment, falls and all-cause mortality in older adults. Methods A literature search using CINAHL, Cochrane Library, Embase and PubMed databases was conducted for randomized controlled trials, prospective and retrospective cohort and case-control studies examining the use of DACEs in subjects ≥65 years with outcomes on falls, cognitive impairment and all-cause mortality. Retrieved articles were published on or before June 2013. Anticholinergic exposure was investigated using drug class, DACE scoring systems (anticholinergic cognitive burden scale, ACB; anticholinergic drug scale, ADS; anticholinergic risk scale, ARS; anticholinergic component of the drug burden index, DBIAC) or assessment of individual DACEs. Meta-analyses were performed to pool the results from individual studies. Results Eighteen studies fulfilled the inclusion criteria (total 124 286 participants). Exposure to DACEs as a class was associated with increased odds of cognitive impairment (OR 1.45, 95% CI 1.16, 1.73). Olanzapine and trazodone were associated with increased odds and risk of falls (OR 2.16, 95% CI 1.05, 4.44; RR 1.79, 95% CI 1.60, 1.97, respectively), but amitriptyline, paroxetine and risperidone were not (RR 1.73, 95% CI 0.81, 2.65; RR 1.80, 95% CI 0.81, 2.79; RR 1.39, 95% CI 0.59, 3.26, respectively). A unit increase in the ACB scale was associated with a doubling in odds of all-cause mortality (OR 2.06, 95% CI 1.82, 2.33) but there were no associations with the DBIAC (OR 0.88, 95% CI 0.55, 1.42) or the ARS (OR 3.56, 95% CI 0.29, 43.27). Conclusions Certain individual DACEs or increased overall DACE exposure may increase the risks of cognitive impairment, falls and all-cause mortality in older adults. PMID:25735839

  19. The scopolamine-reversal paradigm in rats and monkeys: the importance of computer-assisted operant-conditioning memory tasks for screening drug candidates.

    PubMed

    Buccafusco, Jerry J; Terry, Alvin V; Webster, Scott J; Martin, Daniel; Hohnadel, Elizabeth J; Bouchard, Kristy A; Warner, Samantha E

    2008-08-01

    The scopolamine-reversal model is enjoying a resurgence of interest in clinical studies as a reversible pharmacological model for Alzheimer's disease (AD). The cognitive impairment associated with scopolamine is similar to that in AD. The scopolamine model is not simply a cholinergic model, as it can be reversed by drugs that are noncholinergic cognition-enhancing agents. The objective of the study was to determine relevance of computer-assisted operant-conditioning tasks in the scopolamine-reversal model in rats and monkeys. Rats were evaluated for their acquisition of a spatial reference memory task in the Morris water maze. A separate cohort was proficient in performance of an automated delayed stimulus discrimination task (DSDT). Rhesus monkeys were proficient in the performance of an automated delayed matching-to-sample task (DMTS). The AD drug donepezil was evaluated for its ability to reverse the decrements in accuracy induced by scopolamine administration in all three tasks. In the DSDT and DMTS tasks, the effects of donepezil were delay (retention interval)-dependent, affecting primarily short delay trials. Donepezil produced significant but partial reversals of the scopolamine-induced impairment in task accuracies after 2 mg/kg in the water maze, after 1 mg/kg in the DSDT, and after 50 microg/kg in the DMTS task. The two operant-conditioning tasks (DSDT and DMTS) provided data most in keeping with those reported in clinical studies with these drugs. The model applied to nonhuman primates provides an excellent transitional model for new cognition-enhancing drugs before clinical trials.

  20. No effect of the anticholinergic drugs trihexyphenidyl and biperiden on the plasma concentrations of bromperidol and its reduced metabolite.

    PubMed

    Otani, K; Ishida, M; Yasui, N; Kondo, T; Mihara, K; Suzuki, A; Kaneko, S; Inoue, Y; Shibata, M; Ikeda, K

    1997-04-01

    Effects of the anticholinergic drugs trihexyphenidyl and biperiden on plasma concentrations of bromperidol and its reduced metabolite were studied. Subjects comprised 20 schizophrenic inpatients taking bromperidol, 6-18 mg/ day for 1-9 weeks. Patients were randomly allocated to one of two treatment sequences: trihexyphenidyl-biperiden (n = 12) or biperiden-trihexyphenidyl (n = 8). Each sequence consisted of two 2-week phases, with no washout period between the two phases. The daily dose of trihexyphenidyl was 8 mg and that of biperiden 6 mg. Plasma concentrations of bromperidol and reduced bromperidol were measured using high-performance liquid chromatography (HPLC). There was no significant difference in plasma bromperidol or reduced bromperidol concentrations among baseline, trihexyphenidyl and biperiden phases: 7.3 +/- 3.7 versus 7.2 +/- 4.1 versus 7.0 +/- 4.3 ng/ml and 2.0 +/- 2.1 versus 2.2 +/- 2.1 versus 1.9 +/- 2.0 ng/ml, respectively. The present study thus suggests that neither trihexyphenidyl nor biperiden affects plasma concentrations of bromperidol and its reduced metabolite.

  1. No Neuromuscular Side-Effects of Scopolamine in Sensorimotor Control and Force-Generating Capacity Among Parabolic Fliers

    NASA Astrophysics Data System (ADS)

    Ritzmann, Ramona; Freyler, Kathrin; Krause, Anne; Gollhofer, Albert

    2016-10-01

    Scopolamine is used to counteract motion sickness in parabolic flight (PF) experiments. Although the drug's anticholinergic properties effectively impede vomiting, recent studies document other sensory side-effects in the central nervous system that may considerably influence sensorimotor performance. This study aimed to quantify such effects in order to determine if they are of methodological and operational significance for sensorimotor control. Ten subjects of a PF campaign received a weight-sex-based dose of a subcutaneous scopolamine injection. Sensorimotor performance was recorded before medication, 20min, 2h and 4h after injection in four space-relevant paradigms: balance control in one-leg stance with eyes open (protocol 1) and closed as well as force-generating capacity in countermovement jumps and hops (protocol 2). Postural sway, forces and joint angles were recorded. Neuromuscular control was assessed by electromyography and peripheral nerve stimulation; H-reflexes and M-waves were used to monitor spinal excitability of the Ia afferent reflex circuitry and maximal motor output. (1) H-reflex amplitudes, latencies and functional reflexes remained unchanged after scopolamine injection. (2) M-waves, neuromuscular activation intensities and antagonistic muscle coordination did not change with scopolamine administration. (3) Balance performance and force-generating capacity were not impeded by scopolamine. We found no evidence for changes in sensorimotor control in response to scopolamine injection. Sensory processing of daily relevant reflexes, spinal excitability, maximal motor output and performance parameters were not sensitive to the medication. We conclude that scopolamine administration can be used to counteract motion sickness in PF without methodological and operational concerns or interference regarding sensorimotor skills associated with neuromuscular control.

  2. A pilot randomized clinical trial utilizing the drug burden index to reduce exposure to anticholinergic and sedative medications in older people.

    PubMed

    Gnjidic, Danijela; Le Couteur, David G; Abernethy, Darrell R; Hilmer, Sarah N

    2010-11-01

    The drug burden index (DBI) is an evidence-based tool that utilizes pharmacologic principles to calculate an individual's total exposure to anticholinergic and sedative medications. Higher DBI has been associated with functional impairment in observational studies of older people. To assess the impact of providing information about DBI to general practitioners (GPs) on prescribing for older people. This was a cluster randomized controlled trial with 3 months of follow-up. Participants were volunteers aged ≥70 years, living in self-care retirement villages in Sydney, Australia. The study intervention involved a letter and phone call to GPs, using DBI to prompt them to consider cessation or dose reduction of anticholinergic and sedative medications. The primary study outcome was to assess the impact of information about DBI on prescribing practices of the GPs. A total of 115 participants were enrolled, 57 in the intervention group (from 6 sites) and 58 in the control group (from 6 sites). At baseline, 19 of 57 participants in the intervention group and 31 of 58 participants in the control group had a DBI >0 (p < 0.05). At follow-up, a DBI change was observed in 16 participants. DBI decreased in 12 participants, 6 (32%) in the intervention group, and 6 (19%) in the control group. GPs identified the following barriers to reducing anticholinergic and sedative drugs: uncomfortable altering prescriptions initiated by specialists; unable to influence patients' attitudes; unaware of patients' medications and strong clinical indication. The intervention targeting GPs' prescribing practices was less effective than anticipated in reducing anticholinergic and sedative drug exposure, and barriers were identified. Future studies should explore multidisciplinary interventions, engaging patients, specialists, GPs, and pharmacists.

  3. Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies.

    PubMed

    Wouters, Hans; van der Meer, Helene; Taxis, Katja

    2017-03-01

    The Drug Burden Index (DBI) is a non-invasive method to quantify patients' anticholinergic and sedative drug burden from their prescriptions. This systematic review aimed to summarise the evidence on the associations between the DBI and clinical outcomes and methodological quality of studies. A search in PubMed and Embase (search terms: 'drug', 'burden', and 'index') was performed and experts were contacted. We excluded publications that did not report empirical results or clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. Potential omissions of relevant clinical outcomes and populations were studied. Of the 2998 identified publications, 21 were eligible. Overall, methodological quality of studies was good. In all but one study, adjustment was made for prevalent co-morbidity. The DBI was examined in diverse older individuals, i.e. both males and females from different settings and countries. However, no studies were conducted in other relevant patient groups, e.g. psychiatric patients. Exposure to anticholinergic and sedative drugs was thoroughly ascertained, though the specific calculation of the DBI differed across studies. Outcomes were assessed from medical records, record linkage or validated objective tests or questionnaires. Many studies found associations between the DBI and outcomes including hospitalisation, physical and cognitive function. Cognitive function and quality of life were understudied and the number and scope of longitudinal studies was limited. An accumulating body of evidence supports the validity of the DBI. Longitudinal studies of cognitive function and quality of life and in other patient groups, e.g. psychiatric patients, are warranted.

  4. Effect of food and anti-cholinergic drugs on the pattern of rectosigmoid contractions.

    PubMed Central

    Daly, J; Bergin, A; Sun, W M; Read, N W

    1993-01-01

    The colonic response to a meal is often used to test the effect of drugs on colonic motility, but this test is hindered by its inconsistency. This study has used multiple manometric sensors situated in the rectosigmoid region to investigate whether recording of the site and type of contraction offers a clear discrimination of the colonic response to a meal and the effect of drugs. Two studies were carried out on 16 healthy volunteers. Before the meal, rectosigmoid motility consisted mainly of isolated contractions occurring in a single manometric channel. The motility index increased in every subject after the meal (p < 0.05), but this increase entirely consisted of a massive increase in contractions occurring simultaneously in three or more manometric channels (multiple channel contractions), the number increasing from 9 per hour preprandially to 57 per hour (p < 0.01). There was a concomitant decrease in the number of the single channel contractions from 65 to 56 per hour. In a second study an infusion of an antispasmodic drug, mebeverine hydrochloride, into the sigmoid colon of healthy volunteers stopped the postprandial increase in the multiple channel contractions and prevented the significant rise in the motility index. The decrease in single channel contractions was unaffected. These results show that the colonic response to a meal consists of a change in the pattern of rectosigmoid contractions and suggest that multiple channel contractions may be a more sensitive indicator of the effect of a meal on the rectosigmoid colon than the motility index. PMID:8314512

  5. Towards an animal model of an antipsychotic drug-resistant cognitive impairment in schizophrenia: scopolamine induces abnormally persistent latent inhibition, which can be reversed by cognitive enhancers but not by antipsychotic drugs.

    PubMed

    Barak, Segev; Weiner, Ina

    2009-03-01

    Schizophrenia symptoms segregate into positive, negative and cognitive, which exhibit differential sensitivity to drugs. Recent efforts to identify treatments targeting cognitive impairments in schizophrenia have directed attention to the cholinergic system for its well documented role in cognition. Relatedly, muscarinic antagonists (e.g. scopolamine) produce an 'antimuscarinic syndrome', characterized by psychosis and cognitive impairments. Latent inhibition (LI) is the poorer conditioning to a stimulus resulting from its non-reinforced pre-exposure. LI indexes the ability to ignore irrelevant stimuli and aberrations of this capacity produced by pro-psychotic agents (e.g. amphetamine, MK-801) are used extensively to model attentional impairments in schizophrenia. We recently showed that LI was disrupted by scopolamine at low doses, and this was reversed by typical and atypical antipsychotic drugs (APDs) and the acetylcholinesterase inhibitor physostigmine. Here, at a higher dose (1.5 mg/kg), scopolamine produced an opposite pole of attentional impairment, namely, attentional perseveration, whereby scopolamine-treated rats persisted in expressing LI under strong conditioning that prevented LI expression in controls. Scopolamine-induced persistent LI was reversed by cholinergic and glycinergic cognitive enhancers (physostigmine and glycine) but was resistant to both typical and atypical APDs (haloperidol and clozapine). The latter sets scopolamine-induced persistent LI apart from scopolamine- and amphetamine-induced disrupted LI, which are reversed by both typical and atypical APDs, as well as from other cases of abnormally persistent LI including MK-801-induced persistent LI, which is reversed by atypical APDs. Thus, scopolamine-induced persistent LI may provide a pharmacological LI model for screening cognitive enhancers that are efficient for the treatment of APD-resistant cognitive impairments in schizophrenia.

  6. Synergistic effects of the anti-cholinergic R,R-glycopyrrolate with anti-inflammatory drugs.

    PubMed

    Pahl, Andreas; Bauhofer, Artur; Petzold, Ursula; Cnota, Peter J; Maus, Joachim; Brune, Kay; Szelenyi, Stefan

    2006-12-15

    Currently, much effort is geared towards developing therapies that impact on the inflammation in respiratory diseases such as asthma and COPD, assuming that this will improve disease pathology. R,R-Glycopyrrolate, a quaternary ammonium compound, is a muscarinic receptor antagonist with the potential to be used as a long-acting bronchodilator in patients with asthma and COPD. In this study we evaluated whether the combination of R,R-glycopyrrolate with known anti-inflammatory drugs results in synergistic effects. Human primary monocytes were used as an in vitro model system. M3, M4, M1 and M2 receptors were expressed in these cells in descending order. The combinatory effects of the drugs on the release of TNF-alpha after lipopolysaccharide stimulation were analyzed. R,R-Glycopyrrolate alone did not affect LPS induced TNF-alpha release. The PDE4 inhibitor rolipram dose dependently inhibited the TNF-alpha release. Maximum inhibition was around 70%. The IC(35) for rolipram was 68.9+/-15.2 nM. The simultaneous administration of 10 microM R,R-glycopyrrolate reduced the IC(35) to 1.70+/-1.18 nM. The anti-histamine azelastine inhibited TNF-alpha release dose dependently. The simultaneous administration of R,R-glycopyrrolate did not influence the action of azelastine. The corticosteroid budesonide inhibited the TNF-alpha release dose dependently with an IC(50) of 0.55+/-0.13 nM. The simultaneous administration of 10 microM R,R-glycopyrrolate reduced the IC(50) to 0.13+/-0.03 nM. Finally, R,R-glycopyrrolate was most effective in the triple combination with budesonide and rolipram in the reduction of TNF-alpha release. In conclusion, R,R-glycopyrrolate acts synergistically with the PDE4 inhibitor rolipram and the steroid budesonide in inhibiting inflammatory mediators.

  7. β₂ long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD.

    PubMed

    Profita, Mirella; Bonanno, Anna; Montalbano, Angela Marina; Albano, Giusy Daniela; Riccobono, Loredana; Siena, Liboria; Ferraro, Maria; Casarosa, Paola; Pieper, Michael Paul; Gjomarkaj, Mark

    2012-07-01

    We quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β(2)-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and TGF-β1 in HS is higher than in HC; 2) ISSs from COPD and HS caused increased neutrophil adhesion to 16-HBE when compared to ISSs from HC. The effect of ISSs from COPD was significantly reduced by TGF-β1 depletion or by the pretreatment with Olodaterol or Tiotropium alone or in combination, while the effect of ISSs from HS was significantly reduced by the pretreatment with Olodaterol alone; 3) mAChR2, mAChR3 and ChAT expression was increased in 16-HBE stimulated with ISSs from COPD and TGF-β1 depletion significantly reduced this effect on mAChR3 and ChAT expression; 4) rhTGF-β1 increased mAChR2, mAChR3 and ChAT expression in 16-HBE; 5) Olodaterol did not affect the expression of mAChRs and ChAT in 16-HBE. Our findings support the use of β₂ long-acting and anticholinergic drugs to control the bronchoconstriction and TGF-β1-mediated neutrophilic inflammation in COPD. © 2012 Elsevier B.V. All rights reserved.

  8. GABA-ergic but not Anti-Cholinergic Agents Re-induce Clinical Deficits after Stroke

    PubMed Central

    Lazar, Ronald M.; Berman, Mitchell F.; Festa, Joanne R.; Geller, Allison E.; Matejovsky, Teresa G.; Marshall, Randolph S.

    2010-01-01

    Our goal was to determine whether the excitatory (i.e., GABA) neurotransmitter system was important in human stroke recovery. We hypothesized that giving midazolam, a GABAA agonist, to patients would re-induce clinical deficits to a greater extent than the anti-cholinergic scopolamine. Twelve patients (7M) who had recovered from hemiparesis and/or aphasia after first-time stroke and 10 age-matched, healthy controls underwent double-blinded drug challenge with midazolam and 90-days later with scopolamine, or vice versa. Language was scored for comprehension, naming and repetition, and motor function was tested with the 9-Hole Peg Test (9HPT) in each hand. The drugs were administered intravenously in small aliquots until mild awake sedation was achieved. The primary outcome was the change scores from baseline to the two drug conditions, with higher scores denoting greater loss of function. Ten of the 12 patients had recovered from hemiparesis and 7 from aphasia. The median time from stroke to participation was 9.3 months (range = 0.3 – 77.9 months). For motor function, analysis of variance showed that change scores on the 9HPT were significantly greater in patients using the previously paretic hand during the drug state with midazolam (p = .001). Similarly, language change scores were significantly greater among recovered aphasics during the midazolam challenge (p = .01). In our study, patients demonstrated transient re-emergence of former stroke deficits during midazolam but not scopolamine. These data provide beginning clinical evidence for the specificity of GABA-sensitive pathways for stroke recovery. PMID:20172537

  9. GABAergic but not anti-cholinergic agents re-induce clinical deficits after stroke.

    PubMed

    Lazar, Ronald M; Berman, Mitchell F; Festa, Joanne R; Geller, Allison E; Matejovsky, Teresa G; Marshall, Randolph S

    2010-05-15

    Our goal was to determine whether the excitatory (i.e., GABA) neurotransmitter system was important in human stroke recovery. We hypothesized that giving midazolam, a GABA(A) agonist, to patients would re-induce clinical deficits to a greater extent than the anti-cholinergic scopolamine. Twelve patients (7 M) who had recovered from hemiparesis and/or aphasia after first-time stroke and 10 age-matched, healthy controls underwent double-blinded drug challenge with midazolam and 90 days later with scopolamine, or vice versa. Language was scored for comprehension, naming and repetition, and motor function was tested with the 9-Hole Peg Test (9HPT) in each hand. The drugs were administered intravenously in small aliquots until mild awake sedation was achieved. The primary outcome was the change scores from baseline to the two drug conditions, with higher scores denoting greater loss of function. Ten of the 12 patients had recovered from hemiparesis and 7 from aphasia. The median time from stroke to participation was 9.3 months (range=0.3-77.9 months). For motor function, analysis of variance showed that change scores on the 9HPT were significantly greater in patients using the previously paretic hand during the drug state with midazolam (p=0.001). Similarly, language change scores were significantly greater among recovered aphasics during the midazolam challenge (p=0.01). In our study, patients demonstrated transient re-emergence of former stroke deficits during midazolam but not scopolamine. These data provide beginning clinical evidence for the specificity of GABA-sensitive pathways for stroke recovery. Copyright 2010 Elsevier B.V. All rights reserved.

  10. An integrative review of standardized clinical evaluation tool utilization in anticholinergic drug trials for neurogenic lower urinary tract dysfunction

    PubMed Central

    Stothers, L; Tsang, B; Nigro, M; Lazare, D; Macnab, A

    2016-01-01

    Study design: To review prospective and randomized trials studying anticholinergic therapy for neurogenic bladder in SCI to identify whether trials included standardized clinical evaluation tools and reporting measures now recognized to enhance clinical trial data. Methods: A systematic search via EMBASE, MEDLINE, CENTRAL, CINAHL (Cumulative Index to Nursing and Allied Health Literature), HTA (Health Technology Assessment), CMR (Comprehensive Microbial Resource), HAPI (Health and Psychosocial Instruments) and PsycINFO using the key term spinal cord injury crossed with oxybutynin, tolterodine, darifenacin, solifenacin, fesoterodine, trospium chloride, propiverine, propantheline and anticholinergic(s) for 1946–2015 inclusive. We then collated whether standardized clinical tools, measures and descriptors were used within each study identified: American Spine Injury Association (ASIA) impairment scale; symptom scores validated in SCI; technical methodology for urodynamics/video urodynamics; urinary diaries; and standardized urologic terminology. Results: A total of 1225 entries with 610 unique articles were identified, 14 randomized and 16 prospective studies. In 6/30 the population comprised SCI patients with neurogenic bladder alone; the remainder included mixed neurogenic etiologies. Classification using the ASIA impairment scale was used in <10% of studies; none used symptom scores validated in SCI; <50% reported urodynamic test methodology fully, incorporated urinary diaries or used International Continence Society Standardization Subcommittee urinary tract terminology. Conclusion: Integrative review of trials from 1946 to 2015 identified infrequent use of standardized clinical evaluation tools and reporting measures. Data from future trials evaluating therapies for neurogenic bladder would likely be more applicable to specific SCI patients if current standardized classification and descriptors now available were used consistently: for example, the ASIA scale

  11. Scopolamine Transdermal Patch

    MedlinePlus

    ... exposed adhesive layer should be avoided to prevent contamination of fingers with scopolamine. Temporary blurred vision and ... may make you drowsy. Do not drive a car or operate machinery until you know how scopolamine ...

  12. Scopolamine for preventing and treating motion sickness.

    PubMed

    Spinks, A B; Wasiak, J; Villanueva, E V; Bernath, V

    2004-01-01

    Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms have included pharmacological, behavioural and complementary therapies. Although scopolamine has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness. To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology. The Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (OVID, 1966 to March Week 1 2004), EMBASE (1974 to 2004) CINAHL (Ovid, 1982 to March Week 1 2004) and reference lists of retrieved studies were searched for relevant studies. No language restrictions were applied. All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination were included. Outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects were considered. Data from the studies were extracted independently by two authors using standardised forms. Study quality was assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was calculated using the random effects model. Of 27 studies considered potentially relevant, 12 studies enrolling 901 subjects met the entry criteria. Scopolamine was administered via transdermal

  13. Validation of a self-administered instrument to measure adherence to anticholinergic drugs in women with overactive bladder

    PubMed Central

    Andy, UU; Harvie, HS; Smith, AL; Propert, KJ; Bogner, HR; Arya, LA

    2015-01-01

    Aim To validate a self-administered instrument, the Medication Adherence Self-Report Inventory (MASRI) for measuring adherence to anti-cholinergic medication for overactive bladder (OAB). Methods Prospective study in 131 women with OAB treated with fesoterodine. Adherence was measured at 8 and 12 weeks using an interviewer administered Brief Medication Questionnaire (BMQ) that assesses barriers to adherence (criterion standard), the MASRI, and pill count. Construct, concurrent and discriminant validity of the MASRI was assessed. We hypothesized that women who were non-adherent as measured by the MASRI would be more likely to have a belief barrier than women who were adherent to medication. Results Women diagnosed as non-adherent by the MASRI were more likely to report a belief barrier to taking medication as compared to adherent women at 8weeks (80 v 38%, p<0.001) and at 12 weeks (70% v. 40%, p=0.003). Significant correlations were noted between adherence rates measured by the MASRI and the BMQ at 8 weeks (r=0.87, p<0.001) and 12 weeks (r=0.90, p<0.001). Moderate correlation was noted between the adherence rate as measured by the MASRI and pill count at 8 weeks (r=0.49, p=0.02) but not at 12 weeks (r=0.05, p=0.87). The MASRI correctly identified 93% and 96% of non-adherent women at 8 and 12 weeks, respectively. Sensitivity, specificity and positive likelihood ratio of the MASRI for predicting non-adherence was 91%, 82%, and 5.1 at 8 weeks and 90%, 85% and 6.1 at 12 weeks. Conclusions The MASRI is a valid self-administered tool for measuring adherence to anti-cholinergic medication in women with OAB. PMID:24719232

  14. Validation of a self-administered instrument to measure adherence to anticholinergic drugs in women with overactive bladder.

    PubMed

    Andy, Uduak U; Harvie, Heidi S; Smith, Ariana L; Propert, Kathleen J; Bogner, Hillary R; Arya, Lily A

    2015-06-01

    To validate a self-administered instrument, the Medication Adherence Self-Report Inventory (MASRI) for measuring adherence to anti-cholinergic medication for overactive bladder (OAB). Prospective study in 131 women with OAB treated with fesoterodine. Adherence was measured at 8 and 12 weeks using an interviewer administered brief medication questionnaire (BMQ) that assesses barriers to adherence (criterion standard), the MASRI, and pill count. Construct, concurrent and discriminant validity of the MASRI was assessed. We hypothesized that women who were non-adherent as measured by the MASRI would be more likely to have a belief barrier than women who were adherent to medication. Women diagnosed as non-adherent by the MASRI were more likely to report a belief barrier to taking medication as compared to adherent women at 8 weeks (80% vs. 38%, P < 0.001) and at 12 weeks (70% vs. 40%, P = 0.003). Significant correlations were noted between adherence rates measured by the MASRI and the BMQ at 8 weeks (r = 0.87, P < 0.001) and 12 weeks (r = 0.90, P < 0.001). Moderate correlation was noted between the adherence rate as measured by the MASRI and pill count at 8 weeks (r = 0.49, P = 0.02) but not at 12 weeks (r = 0.05, P = 0.87). The MASRI correctly identified 93% and 96% of non-adherent women at 8 and 12 weeks, respectively. Sensitivity, specificity, and positive likelihood ratio of the MASRI for predicting non-adherence was 91%, 82%, and 5.1 at 8 weeks and 90%, 85% and 6.1 at 12 weeks. The MASRI is a valid self-administered tool for measuring adherence to anti-cholinergic medication in women with OAB. © 2014 Wiley Periodicals, Inc.

  15. Comparative studies on the effects of the nootropic drugs adafenoxate, meclofenoxate and piracetam, and of citicholine on scopolamine-impaired memory, exploratory behavior and physical capabilities (experiments on rats and mice).

    PubMed

    Petkov, V D; Mosharrof, A H; Petkov, V V

    1988-01-01

    The effects of adafenoxate (Adf), meclofenoxate (Mf), piracetam (Pc), and citicholine (CCh) on scopolamine (Scop)--impaired memory and exploratory behavior (experiments on rats) and on physical capabilities (experiments on mice) were studied. In the experiments with scopolamine (2 mg/kg i.p.) we used the step-through passive avoidance method to determine the memory changes. In the case of single treatment with the drugs tested scopolamine was injected immediately after training and Adf, Mf, and CCh at doses of 20 and 100 mg/kg and Pc at a dose of 100 mg/kg were administered immediately after scopolamine. In the case of multiple administration the drugs were applied at the same doses for 7 days before training. Scopolamine was injected immediately after training. Retention tests were given 3 and 24 hours later. All the four drugs tested prevented to a large extent or completely the scopolamine-induced retrograde amnesia. However, significant quantitative differences in the antiamnestic effects of the drugs tested were observed. The effects of the four drugs on exploratory behavior were tested in the Opto Varimex apparatus. After 7-day treatment with the drugs at the doses utilized, the behavior of experimental animals was observed for 10 min, checking out the changes in the frequency of rearing, ambulation, and rotation. Only Adf at a dose of 50 mg/kg significantly decreased rearing and ambulation frequencies; this effect was considered to be an expression of accelerated habituation. The physical capabilities of mice were studied, using the method of treadmill (revolving drum activity cage) training. Before the experiment the mice received orally Adf, Mf, and Pc at a dose of 100 mg/kg or were injected intraperitoneally with CCh at doses of 50 and 100 mg/kg once daily for 7 days. The number of revolutions of the drum cages was counted for 4 hours. Only Pc significantly increased the physical capabilities of mice and much delayed the occurrence of fatigue.

  16. Effect of Scopolamine Butylbromide on Clozapine-induced Hypersalivation in Schizophrenic Patients: A Case Series.

    PubMed

    Takeuchi, Ippei; Suzuki, Tatsuyo; Kishi, Taro; Kanamori, Daisuke; Hanya, Manako; Uno, Junji; Fujita, Kiyoshi; Kamei, Hiroyuki

    2015-04-30

    Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0- 97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/ day) for 4 weeks. At the baseline and after 4 weeks' treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients' Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

  17. Atropinic (Anticholinergic) Burden in Antipsychotic-Treated Patients.

    PubMed

    Montastruc, François; Benevent, Justine; Touafchia, Anthony; Chebane, Leila; Araujo, Mélanie; Guitton-Bondon, Emmanuelle; Durrieu, Geneviève; Arbus, Christophe; Schmitt, Laurent; Begaud, Bernard; Montastruc, Jean-Louis

    2017-09-09

    Antipsychotic drugs possess side atropinic (anticholinergic) properties that may induce several adverse drug reactions (ADRs), such as memory loss or cognitive impairment. The aim of the present study was investigating anticholinergic burden in patients treated with antipsychotic drugs. All ADR reports including at least one antipsychotic and registered between 2000 and 2015 in the Midi-Pyrénées PharmacoVigilance Database were extracted and analyzed using the Anticholinergic Duran's list. The primary objective of this cross-sectional study was to calculate anticholinergic burden in antipsychotic-treated patients; the secondary one was to investigate associated factors. Among the 1,948 reports, the average number of atropinic drugs per report was 2.4 ± 1.4. At least one atropinic drug was found in 59.4% of reports (1,158), in addition to antipsychotic drugs. The mean anticholinergic burden per report was 3.9 ± 2.9. A value ≥ 3 was found in 61.7% of the reports. A significant association between anticholinergic burden, age and male gender of patients was found. The mean value of anticholinergic burden remained stable during the study period. This study showed high values of anticholinergic burden in patients receiving antipsychotics. Thus, considering the potential noxious clinical impact of atropinic properties on cognitive functions, an appropriate approach should be to reduce prescription of antipsychotics with a high anticholinergic burden but also coprescription of other frequently associated atropinic drugs, like antiparkinsonians, H1 antihistamines or imipraminic antidepressants in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Scopolamine administration modulates muscarinic, nicotinic and NMDA receptor systems.

    PubMed

    Falsafi, Soheil Keihan; Deli, Alev; Höger, Harald; Pollak, Arnold; Lubec, Gert

    2012-01-01

    Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration.C57BL/6J mice were used for the experiments and divided into four groups. Two groups were given scopolamine 1 mg/kg i.p. (the first group was trained and the second group untrained) in the multiple T-maze (MTM), a paradigm for evaluation of spatial memory. Likewise, vehicle-treated mice were trained or untrained thus serving as controls. Hippocampal levels of M1, nicotinic receptor alpha 4 (Nic4) and 7 (Nic7) and subunit NR1containing complexes were determined by immunoblotting on blue native gel electrophoresis.Vehicle-treated trained mice learned the task and showed memory retrieval on day 8, while scopolamine-treatment led to significant impairment of performance in the MTM. At the day of retrieval, hippocampal levels for M1, Nic7 and NR1 were higher in the scopolamine treated groups than in vehicle-treated groups.The concerted action, i.e. the pattern of four brain receptor complexes regulated by the anticholinergic compound scopolamine, is shown. Insight into probable action mechanisms of scopolamine at the brain receptor complex level in the hippocampus is provided. Scopolamine treatment is a standard approach to test cognitive enhancers and other psychoactive compounds in pharmacological studies and therefore knowledge on mechanisms is of pivotal interest.

  19. Effect of sequence of administration on the pharmacokinetic interaction between the anticholinergic drug biperiden and [3H]quinuclidinyl benzylate or [3H]N-methylscopolamine in rats.

    PubMed

    Ishizaki, J; Yokogawa, K; Nakashima, E; Takayasu, T; Ohshima, T; Ichimura, F

    1998-02-01

    In rats the pharmacokinetic interactions between the anticholinergic drug biperiden and [3H]quinuclidinyl benzylate ([3H]QNB) or [3H]N-methylscopolamine ([3H]NMS) is affected by the sequence in which the drugs are administered. Drug concentrations in various tissues were determined after intravenous administration of [3H]QNB or [3H]NMS (325 ng kg(-1)). Biperiden (6.4 mg kg(-1)) was administered either 5 min before, concomitantly with or 20 min after injection of [3H]QNB or [3H]NMS. When biperiden was administered concomitantly with or before [3H]QNB, distribution of [3H]QNB among the regions of the brain and other tissues was reduced; at 4 h the ratio of the distribution of [3H]QNB for experimental animals to that for control animals ranged from 0.15 to 0.9. When biperiden was administered after [3H]QNB, the distribution of [3H]QNB in the brain and other tissues was significantly higher than for the other two treatments (P < 0.01). However, for [3H]NMS the sequence of administration had no effect on the distribution of the drug in the brain and other tissues except for the kidney. In-vitro, in crude synaptosomal membranes, the amount of [3H]QNB at 2 h relative to the control concentration at equilibrium was 87% when biperiden was added before [3H]QNB and 56% when biperiden was added after [3H]QNB. In both instances the concentration of [3H]NMS reached equilibrium within 30 min. These findings suggest that the difference between the rate constant of association and dissociation at the possible site of action gives rise to the effect of the sequence of administration on the pharmacokinetic interaction.

  20. A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice.

    PubMed

    Kassa, Jirí; Vachek, J

    2002-08-15

    The ability of two types of pharmacological pretreatment (pyridostigmine alone or pyridostigmine in combination with two anticholinergic drugs) to increase the resistance of rats and mice against tabun and to increase the therapeutic efficacy of common antidotal treatment of tabun-poisoned rats and mice was compared. A significant decrease in the LD50 values of tabun was observed when mice as well as rats were pretreated with the prophylactic antidotal mixture consisting of pyridostigmine, benactyzine and trihexyphenidyle, designated PANPAL. Pyridostigmine-pretreated rats were also more resistant against acute lethal effects of tabun but pyridostigmine-induced resistance of rats was not so high as PANPAL-induced resistance. In addition, the pharmacological pretreatment with pyridostigmine alone was not able to protect mice against tabun-induced acute toxicity. The pharmacological pretreatment with pyridostigmine alone was able to increase the efficacy of currently used antidotal treatment (obidoxime in combination with atropine and diazepam) of tabun-induced poisoning, but PANPAL-induced increase in the efficacy of the same antidotal treatment was significantly higher than an increase induced by pyridostigmine alone. PANPAL-induced increase in the efficacy of antidotal treatment of tabun poisoning was also observed in mice. These findings confirm that PANPAL pretreatment of tabun-poisoned rats and mice seems to be much more suitable than currently used pyridostigmine alone.

  1. The problems of anticholinergic adverse effects in older patients.

    PubMed

    Feinberg, M

    1993-01-01

    The old saying 'red as a beet, dry as a bone, blind as a bat, hot as a hare, mad as a hatter' is often quoted when describing the autonomic effects of drugs that block the muscarinic cholinergic system. These effects may be subtle or dramatic, yet can be overlooked or discounted as a natural consequence of old age. Elderly patients can be particularly sensitive to the anticholinergic action of drugs because of physiological and pathophysiological changes that often accompany the aging process. The use of multiple drugs, a common finding in older patients, may result in pharmacodynamic and pharmacokinetic drug interactions that heighten anticholinergic effects. While the classic anticholinergic problems of decreased secretions, slowed gastrointestinal motility, blurred vision, increased heart rate, heat intolerance, sedation and possibly mild confusion, may be uncomfortable for a younger patient in relatively good health, these effects can be disastrous for older patients. Even the most common peripheral anticholinergic complaint of dry mouth can reduce the ability to communicate, predispose to malnutrition, promote mucosal damage, denture misfit or dental caries, and increase the risk of serious respiratory infection secondary to loss of antimicrobial activity of saliva. Mydriasis and the inability to accommodate will impair near vision and may precipitate narrow angle glaucoma in predisposed patients, but less obviously could lead to an increased risk of accidents, including falls. Somatic complaints of constipation and urinary hesitancy, could, in the presence of anticholinergic challenge, result in faecal impaction or urinary retention. Cardiac effects may be poorly tolerated. Increases in heart rate may precipitate or worsen angina. Finally, thermoregulatory impairment induced by anticholinergics, which block the ability to sweat, may lead to life threatening hyperthermia. Central anticholinergic effects range from sedation, mild confusion and inability to

  2. Anticholinergic prescription: are healthcare professionals the real burden?

    PubMed

    Araklitis, George; Thiagamoorthy, Ganesh; Hunter, Jo; Rantell, Angie; Robinson, Dudley; Cardozo, Linda

    2017-08-01

    Anticholinergic medication is the medical treatment for overactive bladder (OAB). These drugs can act on the central nervous system and can lead to cognitive decline, dementia, and potentially death. Patients taking drugs with anticholinergic effects increase their anticholinergic burden-defined as the cumulative effect of taking one or more drugs that can have adverse effects. When prescribing anticholinergic medication for the elderly, we must choose the right drug. We aimed to discover the level of understanding on this subject and its application to real clinical practice amongst our healthcare professionals (HCPs). An 18-point questionnaire was distributed to urogynaecologists, general gynaecologists, urologists, geriatricians, general practitioners (GPs), and nurse specialists to assess knowledge on the subject. A total of 96 HCPs completed the questionnaire. The nurse specialists had the highest score in identifying that oxybutynin was the drug most likely to cross the blood-brain barrier (BBB). The urogynaecologists had the highest score in identifying that trospium chloride was least likely to cross the BBB, whereas the GPs had the lowest score. Solifenacin was the most popular anticholinergic drug prescribed in the elderly without dementia. Trospium chloride was the most popular drug prescribed in the elderly with dementia. We have found that knowledge is lacking amongst all our HCPs, but especially amongst our first-line doctors, our GPs. Education is key in developing knowledge and safe prescribing, to improve the care we give to our patients.

  3. [CENTRAL ANTICHOLINERGIC... SYNDROME?].

    PubMed

    Danilov, M S; Lebedinskii, K M

    2015-01-01

    While reading special literature in diferent languages the authors noted surprising fact: the term and concept of "central anticholinergic syndrome" is well-known as common anaesthesia complication in German (abbr: ZAS) and partially Spanish sources, but in Russian, English or French literature is used only in toxicological context. Describing etiology, pathogenesis, symptoms, diagnosis and treatment of the complication manifesting with comatose, agitated or shivering forms, the authors analyzing the reasons for such a noticeably diferent approaches to the situation reaching 10% of all the general anaesthesia cases. Probably, ZAS isn't nosologically clearly defined syndrome, but just adverse appearance of one of the fundamental general anaesthesia mechanisms? Anyway, the problem of central cholinergic activity suppression, excessive by its amplitude and/or duration, exists all over the world. German concept of ZAS allows the anaesthesiologist to resolve it on pathogenically generalized basis, while in other professional communities various symptomatic approaches seem to be more common.

  4. Anticholinergic burden and cognitive function in a large German cohort of hospitalized geriatric patients.

    PubMed

    Pfistermeister, Barbara; Tümena, Thomas; Gaßmann, Karl-Günter; Maas, Renke; Fromm, Martin F

    2017-01-01

    Previous studies suggest an association between use of anticholinergic drugs in elderly patients and cognitive impairment. However, there are still limited data on the association of anticholinergic drug use and cognitive impairment as well as contribution of individual drugs to anticholinergic load using large, well-documented patient cohorts treated in geriatric units from Europe. We investigated 797,440 prescriptions to 89,579 hospitalized patients treated in geriatric units within the GiB-DAT database. Data of all patients discharged between 1 January 2013 and 30 June 2015 was included. The Anticholinergic Cognitive Burden (ACB) scale was used to classify anticholinergic drugs as definite (score 2 or 3) and possible anticholinergics (score 1). Cognitive function was determined using Mini-Mental State Examination (MMSE) and the standardized scale for dementia (4D+S). In two multivariable logistic regression models age, sex, number of drugs and ACB total scores were identified as variables independently associated with cognitive impairment as measured by MMSE (odds ratio per ACB unit 1.114, 95% CI 1.099-1.130) or the diagnosis dementia (odds ratio 1.159 per ACB unit, 95% CI 1.144-1.173, both p < 0.0001). High anticholinergic load was associated with patients with severe cognitive impairment (p < 0.05 for all pairwise comparisons). ACB score 3 anticholinergic drugs contributed 77.9% to the cumulative amount of ACB points in patients with an anticholinergic load of 3 and higher. Using a cross-sectional study design, a significant positive association between anticholinergic drug load and cognitive impairment in European patients treated in specialised geriatric units was found. The most frequently used definitve anticholinergic drugs were quetiapine, amitriptyline and carbamazepine.

  5. Anticholinergic burden and cognitive function in a large German cohort of hospitalized geriatric patients

    PubMed Central

    Pfistermeister, Barbara; Tümena, Thomas; Gaßmann, Karl-Günter; Maas, Renke; Fromm, Martin F.

    2017-01-01

    Purpose Previous studies suggest an association between use of anticholinergic drugs in elderly patients and cognitive impairment. However, there are still limited data on the association of anticholinergic drug use and cognitive impairment as well as contribution of individual drugs to anticholinergic load using large, well-documented patient cohorts treated in geriatric units from Europe. Methods We investigated 797,440 prescriptions to 89,579 hospitalized patients treated in geriatric units within the GiB-DAT database. Data of all patients discharged between 1 January 2013 and 30 June 2015 was included. The Anticholinergic Cognitive Burden (ACB) scale was used to classify anticholinergic drugs as definite (score 2 or 3) and possible anticholinergics (score 1). Cognitive function was determined using Mini-Mental State Examination (MMSE) and the standardized scale for dementia (4D+S). Results In two multivariable logistic regression models age, sex, number of drugs and ACB total scores were identified as variables independently associated with cognitive impairment as measured by MMSE (odds ratio per ACB unit 1.114, 95% CI 1.099–1.130) or the diagnosis dementia (odds ratio 1.159 per ACB unit, 95% CI 1.144–1.173, both p < 0.0001). High anticholinergic load was associated with patients with severe cognitive impairment (p < 0.05 for all pairwise comparisons). ACB score 3 anticholinergic drugs contributed 77.9% to the cumulative amount of ACB points in patients with an anticholinergic load of 3 and higher. Conclusions Using a cross-sectional study design, a significant positive association between anticholinergic drug load and cognitive impairment in European patients treated in specialised geriatric units was found. The most frequently used definitve anticholinergic drugs were quetiapine, amitriptyline and carbamazepine. PMID:28187171

  6. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    NASA Technical Reports Server (NTRS)

    Wu, L.; Tam, V.; Chow, Diana S. L.; Putcha, Lakshmi

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND). The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial with INSCOP.

  7. Atropine and Other Anticholinergic Drugs

    DTIC Science & Technology

    2007-01-01

    compromise near- who first analyzed the pharmacology and toxicol- vision in the case of accidental use. Military re- ogy of tabun obtained from captured...Lipp JA and Dola TJ (1978). Effect of atropine upon 290-293. the cerebrovascular system during soman-induced NakajimaT.Ohta S. Morita H etal. (1997...sarin: Clinical manifes- Wills JH (1963). Pharmacological antagonists of the tations and treatment of accidental poisoning by anticholinesterase agents

  8. [The first labor analgesia with drug was already performed in late Meiji-Period (1868-1912): trace of opioid-scopolamine which was used in Akiko Yosano, back to its origins].

    PubMed

    Okutomi, Toshiyuki

    2013-02-01

    There have been some records of labor analgesia with intravenous or rectal anesthetics in early Showa-period (1926-1989). However, the author found that labor analgesia had been already attempted for some women in late Meiji-period (1868-1912). One of agents used was pantopon, a water-soluble opioid without serious respiratory depression as morphine. The drug was developed and produced in Germany. Some doctors applied this agent with scopolamine to labor analgesia in Europe. They also reported that this combination also conferred excellent analgesic effects without any serious complications in the mother and fetus. This combination was originally used for general surgery with inhaled anesthesia at that period. It remains uncertain how Japanese doctors got pantopon scopolamine from Germany.

  9. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    NASA Technical Reports Server (NTRS)

    Wu, L.; Chow, D. S. L.; Tam, V.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials for an Investigative New Drug (IND). The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial with INSCOP. METHODS: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model discrimination was performed, by minimizing the Akaike Information Criteria (AIC), maximizing the coefficient of determination (r²) and by comparison of the quality of fit plots. RESULTS: The best structural model to describe scopolamine disposition after INSCOP administration (minimal AIC =907.2) consisted of one compartment for plasma, saliva and urine respectively that were inter-connected with different rate constants. The estimated values of PK parameters were compiled in Table 1. The model fitting exercises revealed a nonlinear PK for scopolamine between plasma and saliva compartments for K21, Vmax and Km. CONCLUSION: PK model for INSCOP was developed and for the first time it satisfactorily predicted the PK of scopolamine in plasma, saliva and urine after INSCOP administration. Using non-linear PK yielded the best structural model to describe scopolamine disposition between plasma and saliva compartments, and inclusion of non-linear PK resulted in a significant improved model fitting. The model can be utilized to predict scopolamine plasma concentration using saliva and/or urine data that

  10. Pro-oxidant activity of zuclopenthixol in vivo: differential effect of the drug on brain oxidative status of scopolamine-treated rats.

    PubMed

    Khalifa, Amani E

    2004-08-01

    Several clinical studies implicated oxidative stress in the pathophysiology of both psychosis and dementia. As dementia is commonly associated with psychosis, antipsychotic medications are of importance in the pharmacotherapy of dementia particularly as a number of antipsychotics were reported to demonstrate neuronal pro-oxidant and/or antioxidant properties. Impairment of learning and memory, as the most characteristic manifestation of dementia, could be induced in experimental animals by acute administration of scopolamine (SCO) with a resultant elevation in brain oxidative status. This study investigated the potential pro-oxidant and/or antioxidant activity of the antipsychotic drug zuclopenthixol acetate, as its effect on brain oxidative status has yet to be evaluated. A 2 x 3 between-subjects factorial design was used to investigate the simultaneous and interactive effects of zuclopenthixol (0.7 and 1.4 mg/kg i.p.) and SCO on rat brain malondialdehyde, glutathione, glutathione peroxidase and superoxide dismutase levels/activities. Results revealed a significant pro-oxidant effect for both zuclopenthixol and SCO alone conditions. In addition, combined treatment of zuclopenthixol and SCO was found to be significantly different compared to either treatment conditions with regard to their effect on different brain oxidative stress indices. Such findings may have valuable implications in the pharmacotherapy of both psychosis and dementia.

  11. Investigation of anti-motion sickness drugs in the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Cheung, B. S.; Money, K. E.; Kohl, R. L.; Kinter, L. B.

    1992-01-01

    Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

  12. Investigation of anti-motion sickness drugs in the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Cheung, B. S.; Money, K. E.; Kohl, R. L.; Kinter, L. B.

    1992-01-01

    Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

  13. Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

    PubMed

    Wu, Lei; Boyd, Jason L; Daniels, Vernie; Wang, Zuwei; Chow, Diana S-L; Putcha, Lakshmi

    2015-02-01

    Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness.

  14. Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model.

    PubMed

    Yoshiyama, Yasumasa; Kojima, Ayako; Itoh, Kimiko; Uchiyama, Tomoyuki; Arai, Kimihito

    2012-01-01

    Anticholinergics, and drugs with anticholinergic properties, are widely and frequently prescribed, especially to the elderly. It is well known that these drugs decrease cognitive function and increase the risk of dementia. Although the mechanism of anticholinergic drug-induced cognitive impairment has been assumed to be functionally reduced acetylcholine (ACh) neurotransmission, some data have indicated that anticholinergics might enhance the pathology of Alzheimer's disease. In this study, we investigated the pathological effects of anticholinergics on neurodegeneration. We chronically administered two anticholinergics, trihexyphenidyl (TP) and propiverine (PP) (the latter with less central anticholinergic action), to neurodegenerative tauopathy model mice 2 to 10 months old. Furthermore, because the ACh nervous system regulates both central and peripheral inflammation, we administered TP or PP to PS19 mice in which we had artificially induced inflammation by lipopolysaccharide injection. Tau pathology, synaptic loss, and neurodegeneration in the hippocampal region, as well as tau insolubility and phosphorylation, were markedly increased in TP-treated mice and mildly increased in PP-treated mice. Furthermore, immunohistochemical analysis revealed microglial proliferation and activation. Moreover, anticholinergics increased interleukin-1β expression in both the spleen and brain of the tauopathy model mice intraperitoneally injected with lipopolysaccharide to induce systemic inflammation. Interestingly, these alterations were more strongly observed in TP-treated mice than in PP-treated mice, consistent with the level of central anticholinergic action. Anticholinergic drugs not only impair cognitive function by decreased ACh neurotransmission, but also accelerate neurodegeneration by suppressing an ACh-dependent anti-inflammatory system. Anticholinergics should be less readily prescribed to reduce the risk of dementia.

  15. Temporal trends in anticholinergic medication prescription in older people: repeated cross-sectional analysis of population prescribing data.

    PubMed

    Sumukadas, Deepa; McMurdo, Marion E T; Mangoni, Arduino A; Guthrie, Bruce

    2014-07-01

    in older people, medications with anticholinergic (antimuscarinic) effects are associated with adverse clinical outcomes, the risk increasing with increasing anticholinergic exposure. Many anticholinergics are recognised as potentially inappropriate and efforts to reduce prescription have been ongoing. We examined temporal trends of anticholinergic prescription and exposure in older people. : anonymised data on all prescribed medication dispensed to people ≥65 years in Tayside, Scotland were obtained for the years 1995 (n = 67,608) and 2010 (n = 73,465). The Anticholinergic Risk Scale (ARS) was adapted (mARS) to include newer medications and medications identified in other scales as having moderate to strong anticholinergic activity. An individual's mARS score was the sum of scores for individual medications. Differences in prescription of anticholinergic medications and mARS scores between 1995 and 2010 were examined. : a significantly higher proportion of older people received any anticholinergic medication in 2010 compared with 1995 (23.7 versus 20.7%; P < 0.001). High anticholinergic exposure (mARS scores ≥3) was seen in 7.3% in 1995 and 9.9% in 2010 (P < 0.001). Prescription of individual anticholinergic medication was small-only three medications were prescribed to >2% of people. The risk of high anticholinergic exposure increased in those with polypharmacy, social deprivation, those living in care homes and women. : despite increasing evidence of adverse outcomes, the proportion of older people prescribed anticholinergic medications and the proportion with a high anticholinergic exposure has increased between 1995 and 2010. Prescription of individual drug is small so cumulative anticholinergic scores may help future efforts to reduce anticholinergic prescription in older people. © The Author 2013. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Working Memory in the Odor Span Task: Effects of Chlordiazepoxide, Dizocilpine (MK801), Morphine and Scopolamine

    PubMed Central

    Galizio, Mark; Deal, Melissa; Hawkey, Andrew; April, Brooke

    2012-01-01

    Rationale A number of tasks are used to assess working memory in rodents, but the Odor Span task (OST) is unique in studying performance as a function of the number of stimuli to remember. Objectives The purpose of the present study was to better characterize the behavioral pharmacology of the OST by exploring the effects of several amnestic agents including an NMDA antagonist (dizocilpine), a positive GABA-A modulator (chlordiazepoxide), an anticholinergic compound (scopolamine) and as a negative control, an opiate receptor agonist (morphine). Methods Rats were trained to perform on the OST which is a non-match-to-sample procedure with an incrementing number of sample odors to remember as the session progresses. Trials with a simple odor discrimination task (SD) were interspersed to provide a control for effects unrelated to memory load. Results All four drugs disrupted performances on the OST task in a dose-dependent fashion, but only the NMDA antagonist dizocilpine produced impairments that were clearly dependent on the number of stimuli to remember. Dizocilpine impaired OST performance at a dose (0.1 mg/kg) that did not affect SD and that impairment depended on memory-load. Chlordiazepoxide (3.0 mg/kg) also produced amnestic effects that were manifest by shorter memory spans and runs of correct responding. In contrast, morphine and scopolamine impaired OST accuracy only at doses that also disrupted SD (18.0 and 0.3 mg/kg, respectively). Conclusions These results provide evidence of NMDA and benzodiazepine modulation of working memory as assessed by the OST. PMID:22918519

  17. [Oral anticholinergics in overactive bladder].

    PubMed

    Madersbacher, H

    2006-07-01

    Behavioural therapy and anticholinergics are the mainstays in the treatment of symptoms of overactive bladder in patients with idiopathic and neurogenic detrusor overactivity; they are the first-line treatment. Oxybutynin, propiverine, tolterodine and trospium chloride as well as the "newcomers" solifenacin and darifenacin are comparable in regards to their efficacy. However, based on different pharmacokinetics and pharmacodynamics with different resorption velocity, different metabolisation and different CNS penetration, the profile of adverse events is different, qualitatively and quantitatively. Substances that are resorbed slowly or available as slow-release formulations are tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier may compromise cognitive functions, especially in geriatric patients, who are already on cholinesterase inhibitors due to memory disorders. The following article gives an overview of the anticholinergics currently prescribed in patients with symptoms of overactive bladder with special attention to the influence of pharmacokinetics/pharmacodynamics on the adverse events profile including possible CNS side effects.

  18. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine.

    PubMed

    Renner, Ulf D; Oertel, Reinhard; Kirch, Wilhelm

    2005-10-01

    The alkaloid L-(-)-scopolamine [L-(-)-hyoscine] competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. The parasympatholytic scopolamine, structurally very similar to atropine (racemate of hyoscyamine), is used in conditions requiring decreased parasympathetic activity, primarily for its effect on the eye, gastrointestinal tract, heart, and salivary and bronchial secretion glands, and in special circumstances for a CNS action. Therefore, scopolamine is most suitable for premedication before anesthesia and for antiemetic effects. This alkaloid is the most effective single agent to prevent motion sickness. Scopolamine was the first drug to be made commercially available in a transdermal therapeutic system (TTS-patch) delivering alkaloid. Recently, pharmacokinetic data on scopolamine in different biozlogic matrices were obtained most efficiently using liquid chromatographic-tandem mass spectrometric (LC-MS/MS) or gas chromatography online coupled to mass spectrometry. Pharmacokinetic parameters are dependent on the dosage form (oral dose, tablets; parenteral application; IV infusion; SC and IM injection). Scopolamine has a limited bioavailability if orally administered. The maximum drug concentration occurs approximately 0.5 hours after oral administration. Because only 2.6% of nonmetabolized L-(-)-scopolamine is excreted in urine, a first-pass metabolism is suggested to occur after oral administration of scopolamine. Because of its short half-life in plasma and dose-dependent adverse effects (in particular hallucinations and the less serious reactions, eg, vertigo, dry mouth, drowsiness), the clinical use of scopolamine administered orally or parenterally is limited. To minimize the relatively high incidence of side effects, the transdermal dosage form has been developed. The commercially available TTS

  19. Treatment of motion sickness in parabolic flight with buccal scopolamine

    NASA Technical Reports Server (NTRS)

    Norfleet, William T.; Degioanni, Joseph J.; Reschke, Millard F.; Bungo, Michael W.; Kutyna, Frank A.; Homick, Jerry L.; Calkins, D. S.

    1992-01-01

    Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated. Twenty-one subjects flew aboard a KC-135 aircraft operated by NASA which performed parabolic maneuvers resulting in periods of 0-g, 1-g, and 1.8-g. Each subject flew once with a tablet containing scopolamine and once with a placebo in a random order, crossover design. Signs and symptoms of motion sickness were systematically recorded during each parabola by an investigator who was blind to the content of the tablet. Compared with flights using placebo, flights with buccal scopolamine resulted in significantly lower scores for nausea (31-35 percent reduction) and vomiting (50 percent reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. It is concluded that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.

  20. Treatment of motion sickness in parabolic flight with buccal scopolamine

    NASA Technical Reports Server (NTRS)

    Norfleet, William T.; Degioanni, Joseph J.; Reschke, Millard F.; Bungo, Michael W.; Kutyna, Frank A.; Homick, Jerry L.; Calkins, D. S.

    1992-01-01

    Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated. Twenty-one subjects flew aboard a KC-135 aircraft operated by NASA which performed parabolic maneuvers resulting in periods of 0-g, 1-g, and 1.8-g. Each subject flew once with a tablet containing scopolamine and once with a placebo in a random order, crossover design. Signs and symptoms of motion sickness were systematically recorded during each parabola by an investigator who was blind to the content of the tablet. Compared with flights using placebo, flights with buccal scopolamine resulted in significantly lower scores for nausea (31-35 percent reduction) and vomiting (50 percent reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. It is concluded that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.

  1. Anticholinergic poisoning from Jimson weed.

    PubMed

    Mahler, D A

    1976-06-01

    Jimson weed (Datura stramonium), is a wild growing herb that contains belladonna alkaloids. Recently there have been reports of intentional ingestion of Jimson weed by adolescents for psychedelic purposes. When seen in emergency department, these patients appear with physical signs of atropine-like poisoning, disturbances of thought and hallucinations. Diagnosis depends on a positive history, if available, and recognition of anticholinergic effects. Differentiation from lysergic acid diethylamide (LSD) ingestion and schizophrenia is important. Physostigmine, an anticholinergic agent, can reverse both central and peripheral manifestations of Jimson weed intoxication.

  2. Midazolam: An Improved Anticonvulsant Treatment for Nerve Agent-Induced Seizures

    DTIC Science & Technology

    2002-01-01

    several potent anticholinergic drugs ( biperiden , scopolamine, trihexyphenidyl) appeared to be viable candidates for development. It was decided at...benzodiazepines (diazepam or midazolam), along with one of the anticholinergic drugs ( biperiden , scopolamine, trihexyphenidyl) for controlling soman-induced

  3. Systematic review on the use of anticholinergic scales in poly pathological patients.

    PubMed

    Villalba-Moreno, Angela Maria; Alfaro-Lara, Eva Rocío; Pérez-Guerrero, Maria Concepción; Nieto-Martín, Maria Dolores; Santos-Ramos, Bernardo

    2016-01-01

    Anticholinergic drugs may increase the risk of cognitive and functional disorders in older patients. There are anticholinergic scales on which said risk is estimated. The objectives of this study are: to identify the scales described in literature that are applicable to polypathological patients and analyze their clinical outcomes. A systematic review was performed. Data sources were MEDLINE, EMBASE and Web of Science which were consulted until August 2014. (1) studies that specify the list of drugs, describe the methodology for their elaboration and how they calibrate the anticholinergic potential and (2) studies that use the scales identified as a tool to measure exposure to anticholinergic drugs in polypathological patients or those with similar characteristics. The main differences between the scales and main results on cognitive, functional and mortality status were collected. 25 articles were included. 10 scales were identified. For their preparation, 8 were based on literature about drugs with anticholinergic activity and/or previously published scales as well as expert opinions. Exposure to anticholinergic drugs has been linked to cognitive disorders (basically measured with Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive Burden Scale (ACB) and Drug Burden Index (DBI)) and functional scale (with ARS and DBI). However, there is no clear relationship with mortality. The Anticholinergic Drug Scale was the only one that obtained no association with any of the variables studied. There is a great variety of scales published and applied to older patients. The clinical results are different depending on the scale used which is probably due to the different methodology in their elaboration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Participation of the dorsal hippocampus in stimulus discrimination with scopolamine.

    PubMed

    Casasola, C; Mejía-Gervacio, S; Cruz-Pérez, M; Sánchez-Castillo, H; Velázquez-Martínez, D N

    2007-10-31

    Stimulus discrimination is the capacity of an organism to differentiate between stimuli and emit associated responses. The administration of the muscarinic antagonist scopolamine can be used as a stimulus by mammals in a discrimination task. The present study analyzes the contribution of the hippocampus in scopolamine discrimination and generalization. Male Wistar rats, weighing 250-300 g at the beginning of the experiment, were trained to discriminate between scopolamine (1.0 mg/kg, i.p.) and saline administration using a two-lever operant task; rats had to respond differentially to each lever depending on the preceding drug or saline administration. Once stimulus control was attained, rats were tested with different scopolamine doses (0.0, 0.056, 0.091, 0.16, 0.31 and 1.0 mg/kg, i.p.) in order to obtain generalization curves. After generalization the rats were randomly assigned to hippocampal CA1 lesion or control groups. Hippocampus impairment produced a transient decrease in the capacity to discriminate between scopolamine and saline conditions; nonetheless, scopolamine correct responses were rapidly recovered after a few sessions and even maintained after 90 days. Correct responses for saline condition were never recovered. The generalization curve obtained after hippocampus lesion showed a response gradient severely flattened. Results suggest that the hippocampus participates as a neural system supporting the sensitivity to detect discrete changes in stimulus properties and relational memory, more than on the capacity to recall for simple associative responses.

  5. [Anticholinergic burden and delirium in elderly patients during acute hospital admission].

    PubMed

    Rojo-Sanchís, Aurora M; Vélez-Díaz-Pallarés, Manuel; Muñoz García, María; Delgado Silveira, Eva; Bermejo Vicedo, Teresa; Cruz Jentoft, Alfonso

    2016-01-01

    The use of anticholinergic drugs in the elderly has been associated to an increased frequency of delirium. There are different scales for estimating the anticholinergic burden, such as the Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Anticholinergic Cognitive Burden (ACB). The aim of the study is to establish the relationship between anticholinergic burden measured by ADS, ARS, and ACB scales and incident or prevalent delirium. An ambispective observational study was conducted for 76 days in the acute geriatric unit of a tertiary hospital. All patients over 80 years-old were included, except re-admissions or those subjected to palliative care. The data collected included sex, age, chronic medication and any recent changes, recent drugs prescribed prior to an episode of delirium, chronic kidney disease, diabetes mellitus, dementia, visual and auditory impairment, and their combination as sensory impairment, previous falls, stroke, brain tumour, and incident and prevalent delirium. A total of 72 patients were included. Incident delirium was detected in 8.1% of the patients, and prevalent delirium in 40.9%. A statistically significant association was established between anticholinergic drugs and the incident delirium measured by the ARS scale (P=.017). None of the scales was able to establish a significant association with prevalent delirium. The ARS scale was related to new episodes of delirium. All scales were insufficient when it came to establishing an association with prevalent delirium. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Scopolamine in racing horses: trace identifications associated with dietary or environmental exposure.

    PubMed

    Brewer, Kimberly; Dirikolu, Levent; Hughes, Charlie G; Tobin, Thomas

    2014-03-01

    Scopolamine (L-hyoscine) identifications, often in small-number clusters, have been reported worldwide in performance horses over the last 30 years. Scopolamine is an Association of Racing Commissioners International (ARCI) class 3, penalty class B, substance with potential to affect performance. As such, scopolamine identification(s) in race or performance horses can result in significant penalties for the connections of the horse(s). Reviewed here is the worldwide distribution of scopolamine containing plants (primarily Datura spp.), with estimates of their potential toxicity to horses through dietary and/or environmental exposure. Also reviewed are the basic pharmacology of scopolamine and its precursor, urinary concentrations following feedstuff exposure, and the probable pharmacological/forensic significance of such findings. Based on an overview of the world literature on scopolamine, the expected characteristics of inadvertent environmental exposure are also presented with a view to making clear the potential of scopolamine identifications, with or without atropine, as a direct and expected outcome of both the worldwide distribution of scopolamine-containing plants and the sensitivity of modern equine drug testing. It is of particular interest that only 2/30 reported post-event equine identifications of scopolamine have been associated with atropine, suggesting that failure to identify atropine is not a biomarker of pharmaceutical administration of scopolamine. Available quantitative information associated with scopolamine identifications is consistent with the 75 ng/mL regulatory threshold for scopolamine currently used in Louisiana racing in the USA and the 30 ng/mL reporting threshold in effect in European racing.

  7. Toxicological results in a fatal and two non-fatal cases of scopolamine-facilitated robberies.

    PubMed

    Lusthof, K J; Bosman, I J; Kubat, B; Vincenten-van Maanen, M J

    2017-02-04

    The use of scopolamine as an incapacitating drug, in sexual crimes and robberies, has been known for many decades. However, blood concentrations and doses of scopolamine in those cases are largely unknown. Here we present the toxicological results of one fatal and two non-fatal cases in a series of scopolamine-facilitated robberies. In the fatal case, the concentration of scopolamine in heart blood was 0.30mg/L, about 3000 times higher than the average therapeutic level of 0.0001mg/L (for one dermal patch). In femoral blood, the concentration of scopolamine was much lower (0.0048mg/L), but still 50 times higher than therapeutic levels. The scopolamine concentration in the stomach was very high (20mg/kg) as compared to the heart blood and femoral blood, which explains the very high concentration in heart blood by postmortem leakage from the stomach. In the non-fatal case, the scopolamine concentration in serum, obtained 23h after the incident, was 0.00035mg/L. The estimated concentration of scopolamine at the time of the incident is 0.0035mg/L. In the other non-fatal case, scopolamine was detected in urine and in hair.

  8. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  9. Anticholinergic Medication Use and Transition to Delirium in Critically Ill Patients: A Prospective Cohort Study.

    PubMed

    Wolters, Annemiek E; Zaal, Irene J; Veldhuijzen, Dieuwke S; Cremer, Olaf L; Devlin, John W; van Dijk, Diederik; Slooter, Arjen J C

    2015-09-01

    Although cholinergic deficiency is presumed to increase delirium risk and use of medication with anticholinergic properties in the ICU is frequent, the relationship between anticholinergic medication use and delirium in this setting remains unclear. We investigated whether exposure to medication with anticholinergic properties increases the probability of transitioning to delirium in critically ill adults and whether this relationship is affected by age or the presence of acute systemic inflammation. Prospective cohort study. A 32-bed medical-surgical ICU at an academic medical center. Critically ill adults admitted to the ICU for more than 24 hours without an acute neurological disorder or another condition that would hamper delirium assessment. None. Daily anticholinergic burden was calculated for each patient based on the sum of the Anticholinergic Drug Scale score for each medication administered. Daily mental status was classified as "coma," "delirium," or an "awake without delirium" state. The primary outcome, the daily transition from an "awake without delirium" state to "delirium," was analyzed using a first-order Markov model that adjusted for eight covariables. A total of 1,112 patients were evaluated over 9,867 ICU days. The daily median summed Anticholinergic Drug Scale score was 2 (interquartile range, 1-3). The transition from being in an "awake without delirium" state to "delirium" occurred on 562 of ICU days (6%). After correcting for confounding, a one-unit increase in the Anticholinergic Drug Scale score resulted in a nonsignificant increase in the probability of delirium occurring the next day (odds ratio, 1.05; 95% CI, 0.99-1.10). Neither age nor the presence of acute systemic inflammation modified this relationship. Exposure to medication with anticholinergic properties, as defined by the Anticholinergic Drug Scale, does not increase the probability of delirium onset in patients who are awake and not delirious in the ICU.

  10. [Angel trumpets: case report of drug-induced psychosis caused by Brugmansia insigniis].

    PubMed

    Paetzold, W; Schneider, U; Emrich, H M; Oehlschläger, P

    1999-05-01

    A case of a psychosis induced by ingestion of blossoms of the solanum Brugmansia insigniis is presented. This plant is used by young persons as a hallucinogenic drug. The psychopathology of this kind of intoxication has not been documented in the literature up to now. It is characterized by anticholinergic effects (e.g. mydriasis), disturbances of orientation, incoherent thoughts, flight of ideas, tangential thinking illusions, auditory hallucinations (e.g. verbal hallucinations), visual hallucinations and affective lability. In addition to hyoscine (scopolamine) and atropine, hallucinogenic effects may be related to previously identified alkaloids.

  11. Microdialysis pharmacokinetic study of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration.

    PubMed

    Wei, Yan; Ying, Mingzhen; Xu, Shuai; Wang, Feng; Zou, Aifeng; Cao, Shilei; Jiang, Xinguo; Wang, Yajie

    2016-01-01

    The purpose of this study was to investigate the microdialysis pharmacokinetic of scopolamine in plasma, olfactory bulb and vestibule after intranasal administration. The pharmacokinetic study of subcutaneous and oral administration was also performed in rats. From the in vivo results, scopolamine intranasal administration can avoid hepatic first-pass effect. Tmax plasma samples after intranasal administration were significantly faster than oral administration and subcutaneous injection. The relative bioavailability of intranasal administrations was 51.8-70% when compared with subcutaneous injection. Moreover, one can see that in comparison with scopolamine subcutaneous administration, scopolamine intranasal gel and solutions can increased drug target index (DTI) with olfactory bulb 1.69 and 2.05, vestibule 1.80 and 2.15, respectively. The results indicated that scopolamine can be absorbed directly through the olfactory mucosa into the olfactory bulb, and then transported to various brain tissue after intranasal administration, with the characteristics of brain drug delivery.

  12. Experimental motion sickness - Efficacy of transdermal scopolamine plus ephedrine

    NASA Technical Reports Server (NTRS)

    Graybiel, A.; Cramer, D. B.; Wood, C. D.

    1981-01-01

    A double-blind, placebo-controlled study compared the efficacy of transdermal therapeutic system-scopolamine administered alone and combined with ephedrine sulfate given orally in doses of 12.5, 25, and 50 mg. Eight normal male students were exposed to stressful accelerations in a slow-rotation room after receiving 10 apparently identical treatments comprising the four drugs and six placebos. Efficacy of the drug was defined in terms of the placebo range and categorized as beneficial, inconsequential, or detrimental. None of the effects was detrimental. Overall beneficial effects were 60% for transdermal therapeutic system-scopolamine (plus placebo) and 57% for the three transdermal therapeutic system-scopolamine plus ephedrine combinations.

  13. Experimental motion sickness - Efficacy of transdermal scopolamine plus ephedrine

    NASA Technical Reports Server (NTRS)

    Graybiel, A.; Cramer, D. B.; Wood, C. D.

    1981-01-01

    A double-blind, placebo-controlled study compared the efficacy of transdermal therapeutic system-scopolamine administered alone and combined with ephedrine sulfate given orally in doses of 12.5, 25, and 50 mg. Eight normal male students were exposed to stressful accelerations in a slow-rotation room after receiving 10 apparently identical treatments comprising the four drugs and six placebos. Efficacy of the drug was defined in terms of the placebo range and categorized as beneficial, inconsequential, or detrimental. None of the effects was detrimental. Overall beneficial effects were 60% for transdermal therapeutic system-scopolamine (plus placebo) and 57% for the three transdermal therapeutic system-scopolamine plus ephedrine combinations.

  14. Differential neuropsychopharmacological influences of naturally occurring tropane alkaloids anisodamine versus scopolamine.

    PubMed

    Zhang, Wei-Wei; Song, Ming-Ke; Cui, Yong-Yao; Wang, Hao; Zhu, Liang; Niu, Yin-Yao; Yang, Li-Min; Lu, Yang; Chen, Hong-Zhuan

    2008-10-10

    Two naturally occurring tropane alkaloids, anisodamine and scopolamine, structurally dissimilar in one OH group, are well established as muscarinic acetylcholine receptor (mAChR) antagonists in clinic and basic research. However, experimental evidence for central effects of anisodamine is limited and conflicting compared with that of scopolamine. In the present study, Morris water maze test, long-term potentiation (LTP) recording and receptor radioligand binding assays were used to explore the disparity in neuropsychopharmacological influences of anisodamine versus scopolamine and possible mechanisms. Anisodamine, at 10-40-fold higher doses than those of scopolamine, did not produce any spatial cognitive deficits as scopolamine, but tended to improve cognition at the repeated high doses. LTP in vivo was then adopted to predict BBB permeability of the muscarinic antagonists following systemic drug administration. Contrary to scopolamine, anisodamine did not influence the formation of LTP in the CA(1) region of rat hippocampus at 40-fold higher dose than that of scopolamine. Additionally, receptor radioligand binding assays (RRLBA) revealed that the binding affinity of anisodamine to mice brain mAChR was much lower than that of scopolamine. The findings suggested that anisodamine did not impair cognition nor depress LTP primarily due to its poor BBB permeability. This work enlarged knowledge of structure-activity relationship among tropane alkaloids, meanwhile providing evidence for more reasonable drug prescription in clinic.

  15. The use of anticholinergic medications in homebound elderly patients with dementia.

    PubMed

    Chan, Wen-Yi; Setter, Stephen M; Sclar, David Alexander; Salek, Sam; Corbett, Cynthia; Henriksen, Anne L

    2006-05-01

    Identify the number of homebound older adults admitted to a home-based health care agency in 2003 with a diagnosis of dementia. Compare the use of anticholinergic medications in older adults with a diagnosis of dementia to a matched comparison group without a diagnosis of dementia. Retrospective, cohort study. Home health care agency in the eastern part of Washington State serving the homebound. Homebound subjects 60 years of age or older with or without a diagnosis of dementia. N/A. Number of homebound subjects with a diagnosis of dementia. Comparison of those in the group diagnosed with dementia (n = 50) to a matched cohort in the group with no dementia diagnosis (n = 50) in regard to use of drugs with anticholinergic activity. From a population of 1,746 patients served in 2003 who met the study criteria, 107 (6.1%) patients had a diagnosis of dementia. Of these, 50 were studied. Of the subjects with dementia, 62% were prescribed a drug with anticholinergic activity, compared with 80% of subjects without dementia. Fewer patients in the study group were prescribed anticholinergic drugs than in the comparison group. The primary drugs with anticholinergic activity cited most often were olanzapine, hydroxyzine, and mirtazapine. Drugs with anticholinergic activity are used frequently in an older homebound population, irrespective of a dementia diagnosis.

  16. Caffeine attenuates scopolamine-induced memory impairment in humans.

    PubMed

    Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J

    1995-11-01

    Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

  17. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    NASA Technical Reports Server (NTRS)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  18. 2-Phenylethynyl-butyltellurium enhances learning and memory impaired by scopolamine in mice.

    PubMed

    Souza, Ana Cristina G; Bruning, César A; Acker, Carmine I; Neto, José S S; Nogueira, Cristina W

    2013-08-01

    Taking into account the memory-enhancing properties of 2-phenylethynyl-butyltellurium (PEBT) and the constant search for drugs that improve cognitive performance, the present study was designed to investigate the effect of PEBT on cognitive impairment induced by scopolamine in mice. PEBT (10 mg/kg, gavage) was administered to mice 1 h before the probe trial in the Morris water maze task. Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneally) 30 min before the probe trial. PEBT significantly ameliorated the scopolamine-induced impairment of long-term memory, as indicated by a decrease in escape latency and an increase in the number of crossings of the platform location when compared with the amnesic mice. To evaluate the effect of PEBT on different phases of memory (acquisition, consolidation, and retrieval) impaired by scopolamine, the step-down inhibitory avoidance task was used. Scopolamine was administered 30 min before training (acquisition), test (retrieval), or immediately after training (consolidation). PEBT, administered 30 min before scopolamine, increased step-down latency in memory-impaired mice, improving the consolidation and retrieval stages, but not acquisition. No significant alterations in locomotor or exploratory behaviors were found in animals treated with PEBT and/or scopolamine. PEBT improved memory deficits during consolidation and retrieval induced by scopolamine.

  19. Scopolamine and depression: a role for muscarinic antagonism?

    PubMed

    Hasselmann, Helge

    2014-01-01

    Depressive disorders have, for a sizeable extent, proven resilient to pharmacotherapy. Established drugs such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs) often provide inadequate symptom relief and sometimes fail altogether. Recently, interest in antidepressant effects of scopolamine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, has arisen. Initial evidence suggests that scopolamine provides relatively rapid and long-lasting symptom alleviation for unipolar and bipolar depressed patients. At the same time, side effects of medical dosages appear mild and transient in nature. The aim of the present review is to tentatively discuss the antidepressant potential of scopolamine and to outline putative neurobiological pathways. Clearly, mAChR antagonism provides an intriguing novel therapeutical approach for treating depressive disorders.

  20. [Interest of scopolamine as a treatment of major depressive disorder].

    PubMed

    Rigal, A; Mouchabac, S; Peretti, C S

    2016-12-01

    The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic…). In 2006, a pilot study made to evaluate the role of the cholinergic system in cognitive symptoms of depression found unexpected results regarding the antidepressant effect of scopolamine in depressive patients. Since that time other studies have been conducted to evaluate the benefits of treatment with intravenous injections of scopolamine. Our main objective was to evaluate the interest of scopolamine as an antidepressant treatment in depressed populations. We conducted a literature review with the aim of assessing the effectiveness of treatment with scopolamine in uni- and bipolar patients with depressive symptoms. The protocol consisted of two injection blocks (each block consisting of three injections spaced fifteen minutes apart within three to five days) of active ingredient or placebo crossover. The selected patients were between 18 and 45years and had the DSM-IV major depressive disorder or bipolar disorder criteria. Regarding the methods of measurement, the primary endpoint was the reduction in scores of the Montgomery Asberg Depression Rating Scale (MADRS) with a total response defined by a decrease of more than 50 % of the score and remission corresponding to a MADRS score<10. Seven sessions of evaluations were performed. The published results are promising in terms of efficiency with rapid antidepressant effect, a total response rate ranging from 59-64% and a remission rate of between 37 and 55

  1. Catalytic activity of ruthenium(III) on the oxidation of an anticholinergic drug-atropine sulfate monohydrate by copper(III) periodate complex in aqueous alkaline medium - decarboxylation and free radical mechanism.

    PubMed

    Byadagi, Kirthi S; Nandibewoor, Sharanappa T; Chimatadar, Shivamurti A

    2013-01-01

    Atropine sulfate monohydrate (ASM) is an anticholinergic drug, having a wide spectrum of activity. Hence, the kinetics of oxidation of ASM by diperiodatocuperate (DPC) in the presence of micro (10-6) amounts of Ru(III) catalyst has been investigated spectrophotometrically in aqueous alkaline medium at I = 0.50 mol dm-3. The reaction between DPC and ASM exhibits 1:2 stoichiometry (ASM:DPC) i. e., one mole of ASM require two moles of DPC to give products. The main oxidation products were confirmed by spectral studies. The reaction is first order with respect to [DPC] and [Ru(III)], while the order with respect to [ASM] and [OH-] was less than unity. The rates decreased with increase in periodate concentration. The reaction rates revealed that Ru(III) catalyzed reaction was about seven-fold faster than the uncatalyzed reaction. The catalytic constant (KC) was also determined at different temperatures. A plausible mechanism is proposed. The activation parameters with respect to slow step of the mechanism were calculated and the thermodynamic quantities were also determined. Kinetic experiments suggest that [Cu(H2IO6)(H2O)2] is the reactive Cu(III) species and [Ru(H2O)5OH]2+ is the reactive Ru(III) species.

  2. Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly: comparison of the anticholinergic cognitive burden scale and anticholinergic risk scale: results from the REPOSI study.

    PubMed

    Pasina, Luca; Djade, Codjo D; Lucca, Ugo; Nobili, Alessandro; Tettamanti, Mauro; Franchi, Carlotta; Salerno, Francesco; Corrao, Salvatore; Marengoni, Alessandra; Iorio, Alfonso; Marcucci, Maura; Violi, Francesco; Mannucci, Pier Mannuccio

    2013-02-01

    Drugs with anticholinergic effects are associated with adverse events such as delirium and falls as well as cognitive decline and loss of independence. The aim of the study was to evaluate the association between anticholinergic burden and both cognitive and functional status, according to the hypothesis that the cumulative anticholinergic burden, as measured by the Anticholinergic Cognitive Burden (ACB) Scale and Anticholinergic Risk Scale (ARS), increases the risk of cognitive decline and impairs activities of daily living. This cross-sectional, prospective study (3-month telephone follow-up) was conducted in 66 Italian internal medicine and geriatric wards participating in the Registry of Polytherapies SIMI (Società Italiana di Medicina Interna) (REPOSI) study during 2010. The sample included 1,380 inpatients aged 65 years or older. Cognitive status was rated with the Short Blessed Test (SBT) and physical function with the Barthel Index. Each patient's anticholinergic burden was evaluated using the ACB and ARS scores. The mean SBT score for patients treated with anticholinergic drugs was higher than that for patients receiving no anticholinergic medications as also indicated by the ACB scale, even after adjustment for age, sex, education, stroke and transient ischaemic attack [9.2 (95 % CI 8.6-9.9) vs. 8.5 (95 % CI 7.8-9.2); p = 0.05]. There was a dose-response relationship between total ACB score and cognitive impairment. Patients identified by the ARS had more severe cognitive and physical impairment than patients identified by the ACB scale, and the dose-response relationship between this score and ability to perform activities of daily living was clear. No correlation was found with length of hospital stay. Drugs with anticholinergic properties identified by the ACB scale and ARS are associated with worse cognitive and functional performance in elderly patients. The ACB scale might permit a rapid identification of drugs potentially associated with cognitive

  3. Anticholinergics for overactive bladder therapy: central nervous system effects.

    PubMed

    Chancellor, Michael; Boone, Timothy

    2012-02-01

    The mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for "OAB" plus "muscarinic antagonists" or "anticholinergic drug." Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood-brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable. © 2011 Blackwell Publishing Ltd.

  4. Discrimination of Solanaceae taxa and quantification of scopolamine and hyoscyamine by ATR-FTIR spectroscopy.

    PubMed

    Naumann, Annette; Kurtze, Lukas; Krähmer, Andrea; Hagels, Hansjoerg; Schulz, Hartwig

    2014-10-01

    Plant species of the Solanaceae family (nightshades) contain pharmacologically active anticholinergic tropane alkaloids, e.g., scopolamine and hyoscyamine. Tropane alkaloids are of special interest, either as active principles or as starting materials for semisynthetic production of other substances. For genetic evaluation, domestication, cultivation, harvest and post-harvest treatments, quantification of the individual active principles is necessary to monitor industrial processes and the resulting finished products. Up to now, frequently applied methods for quantification are based on high performance liquid chromatography and gas chromatography optionally combined with mass spectrometry. However, alternative analytical methods have the potential to replace the established standard methods partly. In this context, attenuated total reflection-Fourier transform infrared spectroscopy enabled chemotaxonomical classification of the Solanaceae Atropa belladonna, Datura stramonium, Hyoscyamus niger, Solanum dulcamara, and Duboisia in combination with cluster analysis. Also discrimination of genotypes within species was achieved to some extent. The most characteristic scopolamine bands could be identified in attenuated total reflection-Fourier transform infrared spectra of Solanaceae leaves, which allow a fast characterisation of plants with high scopolamine content. Applying a partial least square algorithm, very good calibration statistics were obtained for the prediction of the scopolamine content (residual prediction deviation = 7.67), and moderate prediction quality could be achieved for the hyoscyamine content (residual prediction deviation = 2.48).

  5. [Anticholinergics for overactive bladder: does subtype selectivity play a role?].

    PubMed

    Michel, M C; Barendrecht, M M; Oelke, M

    2006-07-01

    Anticholinergics act in the treatment of overactive bladder by blocking muscarinic receptors of which five subtypes exist. Their desired effects occur via M(3) receptors, but a role for M(2) receptors is being discussed. Adverse effects such as dry mouth and constipation occur also via M(3) receptors, but M(2) and M(1) receptors can mediate side effects in the heart or on cognitive function, respectively. Therefore, an M(3)-selective drug such as darifenacin could theoretically be less effective but also have fewer cardiac or central nervous side effects. However, the limited available clinical data do not support a smaller efficacy or better general tolerability. The lack of adverse effects on cognitive function is well documented for darifenacin, but it cannot yet be determined definitively whether this discriminates it from other modern anticholinergics.

  6. The effect of transdermal scopolamine for the prevention of postoperative nausea and vomiting

    PubMed Central

    Antor, María A.; Uribe, Alberto A.; Erminy-Falcon, Natali; Werner, Joseph G.; Candiotti, Keith A.; Pergolizzi, Joseph V.; Bergese, Sergio D.

    2014-01-01

    Postoperative nausea and vomiting (PONV) is one of the most common and undesirable complaints recorded in as many as 70–80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia (SAMBA) guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 h after surgery. In an effort to find a safer and reliable therapy for PONV, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl) benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a non-selective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2)-scopolamine (tropic acid ester with scopine; MW = 303.4). Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 h. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in PONV. Thus, scopolamine is a promising candidate for the management of PONV in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long-lasting clinical effects. PMID:24782768

  7. The Comparative Peripheral Anticholinergic-Like Adverse Event Profiles of Olanzapine and Risperidone.

    PubMed

    Kennedy, John S.; Bymaster, Frank P.; Basson, Bruce R.; Gilmore, Julie A.; Tran, Pierre V.

    2000-08-01

    OBJECTIVE: To test the hypothesis that reported in vitro muscarinic receptor affinity differences between olanzapine and risperidone would be reflected in peripheral solicited anticholinergic adverse event frequencies. METHOD: Data from a double-blind, randomized trial of olanzapine versus risperidone in 339 patients (age range, 18-65 years) with DSM-IV schizophrenia spectrum acute psychosis were retrospectively analyzed. Subgroups based on the median of the mean daily drug dose were constructed (olanzapine 17 mg; risperidone 6 mg). Mean daily dose of adjunctive anticholinergic medication was compared using ANOVA, and frequencies of treatment-emergent solicited adverse events defined by the Association de Méthodologie et de Documentation en Psychiatrie (AMDP-5) were analyzed using categorical methods. RESULTS: Mean daily anticholinergic dose was significantly higher overall for the risperidone group (0.68 +/- 1.27 mg) than for the olanzapine group (0.27 +/- 0.76 mg) (p =.002). When only patients who did not receive anticholinergic adjunct therapy were considered, no significant differences in the frequency of specific anticholinergic adverse events occurred in olanzapine-treated patients as compared with risperidone-treated patients (p >/=.245). There was also no significant difference between olanzapine and risperidone in the frequency of any anticholinergic adverse event (p =.458). CONCLUSION: At clinically effective doses, olanzapine and risperidone did not differ significantly in frequency of peripheral anticholinergic events. These results support the view that, for olanzapine and risperidone, in vitro anticholinergic receptor binding (K(i) values) may not predict in vivo peripheral events.

  8. Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong.

    PubMed

    Chan, Thomas Y K

    2016-03-18

    In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989-2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989-1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994-1996. In the whole of Hong Kong, the incidence during 2000-June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008-2012 was 0.06 per 100,000 population. Contamination of non-toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures.

  9. Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong

    PubMed Central

    Chan, Thomas Y. K.

    2016-01-01

    In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989–2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989–1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994–1996. In the whole of Hong Kong, the incidence during 2000–June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008–2012 was 0.06 per 100,000 population. Contamination of non-toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures. PMID:26999208

  10. Further evaluation of mechanisms associated with the antidepressant-like signature of scopolamine in mice.

    PubMed

    Martin, Anna E; Schober, Douglas A; Nikolayev, Alexander; Tolstikov, Vladimir V; Anderson, Wesley H; Higgs, Richard E; Kuo, Ming-Shang; Laksmanan, Anastasia; Catlow, John T; Li, Xia; Felder, Christian C; Witkin, Jeffrey M

    2017-03-09

    Conventional antidepressants lack efficacy for many patients (treatment-resistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling. Since the work on these mechanisms with scopolamine has been limited, the present set of experiments was designed to further explore these mechanisms of action. Male, NIH Swiss mice demonstrated a robust and immediate antidepressant signature when studied under the forced-swim test. The AMPA receptor antagonist NBQX prevented this antidepressant-like effect of scopolamine and ketamine. An orally-bioavilable mTOR inhibitor (ADZ8055) also attenuated the antidepressant-like effects of scopolamine and ketamine. Scopolamine was also shown to augment the antidepressant-like effect of the selective serotonin reuptake inhibitor citalopram. When given in combination, scopolamine and ketamine acted synergistically to produce antidepressant-like effects. Although drug interaction data suggested that additional mechanisms might be at play, metabolomic analysis of frontal cortex and plasma from muscarinic M1+/+ and M1 -/- mice given scopolamine or vehicle did not reveal any hints as to the nature of these additional mechanisms of action. Overall, the data substantiate and extend the idea that AMPA and mTOR signaling pathways are necessary for the antidepressant-like effects of scopolamine and ketamine, mechanisms that appear to be of general significance for TRD therapeutic agents.

  11. Rapid determination of scopolamine in evidence of recreational and predatory use.

    PubMed

    Sáiz, Jorge; Mai, Thanh Duc; López, María López; Bartolomé, Carmen; Hauser, Peter C; García-Ruiz, Carmen

    2013-12-01

    In recent years, scopolamine has become a drug of common use for recreational and predatory purposes and several ways of administration have been devised. A method for the rapid analysis of suspicious samples was developed, using a portable capillary electrophoresis with contactless conductivity detection. The method allows the separation of scopolamine from atropine which has a similar structure and is present along with scopolamine in some samples. The method was demonstrated to be useful for the fast analysis of several types of evidential items which have recently been reported to have been abused with fatal consequences or employed for criminal purposes. An infusion of Datura stramonium L., in which scopolamine and atropine naturally coexist, was analyzed for being frequently consumed for recreational purposes. A spiked moisturizing cream and six spiked alcoholic beverages were also analyzed. In spite of the complexity of the specimens, the sample pre-treatment methods developed were simple and fast.

  12. Differential effects of scopolamine and amphetamine on microcomputer-based performance tests

    NASA Technical Reports Server (NTRS)

    Kennedy, Robert S.; Odenheimer, Robert C.; Baltzley, Dennis R.; Dunlap, William P.; Wood, Charles D.

    1990-01-01

    The effects of four weekly treatments with scopolamine (1.0 mg) and d-amphetamine (10 mg), separately or in combination, on human performance were investigated in 16 subjects undergoing nine performance tests from a menu of microcomputer-based tests administered after the treatment. It was d-amphetamine treatment that enhanced the results of motor and perceptual speed tests, while scopolamine had no effect on these tests. Two of the five cognitive tests showed reductions with scopolamine. The effects of scopolamine in this and other studies are considered in terms of a model which implies that the magnitude of the performance deficit depends on the performance type and the dosage level of the drug.

  13. Differential effects of scopolamine and amphetamine on microcomputer-based performance tests

    NASA Technical Reports Server (NTRS)

    Kennedy, Robert S.; Odenheimer, Robert C.; Baltzley, Dennis R.; Dunlap, William P.; Wood, Charles D.

    1990-01-01

    The effects of four weekly treatments with scopolamine (1.0 mg) and d-amphetamine (10 mg), separately or in combination, on human performance were investigated in 16 subjects undergoing nine performance tests from a menu of microcomputer-based tests administered after the treatment. It was d-amphetamine treatment that enhanced the results of motor and perceptual speed tests, while scopolamine had no effect on these tests. Two of the five cognitive tests showed reductions with scopolamine. The effects of scopolamine in this and other studies are considered in terms of a model which implies that the magnitude of the performance deficit depends on the performance type and the dosage level of the drug.

  14. Effects of scopolamine and dextroamphetamine on human performance

    NASA Technical Reports Server (NTRS)

    Schmedtje, John F., Jr.; Oman, Charles M.; Letz, Richard; Baker, Edward L.

    1988-01-01

    The effects of two drugs used to prevent symptoms of motion sickness in the operational environment were examined in this study of human performance as measured by computer-based tests of cognitive and psychomotor skills. Each subject was exposed repetitively to five tests: symbol-digit substitution, simple reaction time, pattern recognition, digit span memory, and pattern memory. Although there have been previous reports of decreases in human performance in similar testing with higher dosages of scopolamine or dextroamphetamine, no significant decrements were observed with the operational-level combined dose used in this study (0.4 mg oral scopolamine and 5.0 mg oral dextroamphetamine.) The controversy over the use of combination drug therapy in this environnment is discussed along with the indications for further research based on the findings.

  15. Effects of scopolamine and dextroamphetamine on human performance

    NASA Technical Reports Server (NTRS)

    Schmedtje, John F., Jr.; Oman, Charles M.; Letz, Richard; Baker, Edward L.

    1988-01-01

    The effects of two drugs used to prevent symptoms of motion sickness in the operational environment were examined in this study of human performance as measured by computer-based tests of cognitive and psychomotor skills. Each subject was exposed repetitively to five tests: symbol-digit substitution, simple reaction time, pattern recognition, digit span memory, and pattern memory. Although there have been previous reports of decreases in human performance in similar testing with higher dosages of scopolamine or dextroamphetamine, no significant decrements were observed with the operational-level combined dose used in this study (0.4 mg oral scopolamine and 5.0 mg oral dextroamphetamine.) The controversy over the use of combination drug therapy in this environnment is discussed along with the indications for further research based on the findings.

  16. Safety and tolerability profiles of anticholinergic agents used for the treatment of overactive bladder.

    PubMed

    Oefelein, Michael G

    2011-09-01

    Anticholinergics are the mainstay of pharmacotherapy for overactive bladder (OAB). The anticholinergics used to treat OAB differ in their pharmacological profiles, which may affect their propensity for causing commonly observed adverse effects. The purpose of this is review is to use published clinical data to evaluate the safety and tolerability of commonly prescribed anticholinergics for OAB, provide a context for safety and tolerability in terms of drug pharmacology, summarize the impact of adverse effects on adherence, and discuss the influence of study design on safety and tolerability outcomes. A MEDLINE search was conducted for the period 1990-2010 to identify studies evaluating mechanisms of action, pharmacological profiles, safety issues and adverse events pertaining to anticholinergics used in the treatment of OAB. Compared with immediate-release preparations, the extended-release, once daily and transdermal formulations are associated with lower rates of anticholinergic adverse effects, due to improved consistency in serum levels. The most significant adverse effects in terms of affecting the use of anticholinergics agents are CNS and cardiac disturbances. CNS issues are associated with pharmacological properties such as serum concentration, blood-brain barrier permeability and active transport, and receptor binding affinity. Cardiac safety (corrected QT interval) is more dependent on specific molecular attributes. However, more common but less bothersome adverse effects associated with systemic blockade of the muscarinic receptors include dry mouth, constipation, headache and blurred vision. A high potential for interaction between anticholinergics and drugs that compete with the same pathways for hepatic metabolism via cytochrome P450 and renal excretion increases the risk of adverse effects for both antimuscarinic and associated medications, especially in the elderly, who are more likely to be taking multiple drugs. This literature review demonstrates

  17. Prevention of experimental motion sickness by scopolamine absorbed through the skin

    NASA Technical Reports Server (NTRS)

    Graybiel, A.; Knepton, J.; Shaw, J.

    1976-01-01

    A double-blind placebo-controlled study compared the efficacy of the antimotion sickness drug scopolamine when administered by oral or transdermal routes. A secondary purpose was to extend our bioassay involving fixed-dose combinations of the homergic drugs promethazine and ephedrine. After receiving 12 apparently identical drug-placebo treatments, eight normal male students were exposed in a slow rotation room to stressful accelerations generated by their execution of 40 head movements out of the plane of the room's rotation at 1 rpm and at 1-rpm increments until either symptoms were experienced (just short of frank motion sickness) or the 27-rpm ceiling on the test was reached. Efficacy of a drug was defined in terms of the placebo-range and categorized as beneficial, inconsequential, or detrimental. The only detrimental effect was with scopolamine given orally. It is concluded that the advantages of the transdermal scopolamine, which include minimal side effects and prolonged effectiveness, deserve full exploitation.

  18. Effect of low-dose scopolamine on autonomic control of the heart

    NASA Technical Reports Server (NTRS)

    Raeder, E. A.; Stys, A.; Cohen, R. J.

    1997-01-01

    Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

  19. Inhibitory avoidance memory deficit induced by scopolamine: interaction with glutamatergic system in the nucleus accumbens.

    PubMed

    Pakpour, Bahareh; Ahmadi, Shamseddin; Nayer-Nouri, Touraj; Oryan, Shahrbanoo; Zarrindast, Mohammad Reza

    2010-12-01

    The possible involvement of N-methyl-D-aspartate (NMDA) receptors of the nucleus accumbens (NAc) in amnesia induced by scopolamine was investigated. An inhibitory (passive) avoidance task was used for memory assessment in male Wistar rats. The results revealed that intra-NAc administration of a nonselective muscarinic acetylcholine antagonist, scopolamine (1 and 2 g/rat) impaired memory consolidation in the animals when tested 24 h later. Post-training intra-NAc administration of NMDA (0.005 and 0.01 g/rat) also impaired memory consolidation, whereas post-training intra-NAc administration of the NMDA receptor antagonist, MK-801 (0.5, 1 and 1.5 g/rat) did not. Intra-NAc co-administration of an ineffective dose of NMDA with ineffective doses of scopolamine (0.25 and 0.5 g/rat) after training had no significant effect on memory consolidation, but intra-NAc injections of effective doses of NMDA (0.005 and 0.01 g/rat) prevented the amnesic effect of an effective dose of scopolamine (2 g/rat). In contrast, intra-NAc co-administration of MK-801 (0.5, 1 and 1.5 g/rat) along with an effective dose of scopolamine (2 g/rat) did not prevent the effect of the latter drug. It can be concluded that NMDA receptors in the NAc are involved in the modulation of memory consolidation that was affected by scopolamine.

  20. Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

    NASA Astrophysics Data System (ADS)

    Kohl, Randall Lee

    Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion ( P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

  1. Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

    NASA Technical Reports Server (NTRS)

    Kohl, Randall Lee

    1986-01-01

    Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, the efficacy of dexamethasone and metyrapone is tested in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80 percent more stressful motion (P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

  2. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  3. Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

    NASA Technical Reports Server (NTRS)

    Putcha, L.; Lei, Wu.; S-L Chow, Diana

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at P<0.05(?OFV=3.84). Results: No significant difference in PK parameters between male and female subjects was observed with 0.1 and 0.2 mg doses. However, CL and Vd were significantly different between male and female subjects at the 0.4 mg dose. Results from population covariate modeling analysis indicate that a onecompartment PK model with first-order elimination rate offers best fit for describing INSCOP concentration-time profiles. The inclusion of sex as a covariate enhanced the model fitting (?OFV=-4.1) owing to the genderdependent CL and Vd differences after the 0.4 mg dose. Conclusion: Statistical modeling of scopolamine concentration-time data suggests gender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose

  4. Population Pharmacokinetics of Intranasal Scopolamine

    NASA Technical Reports Server (NTRS)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  5. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    NASA Technical Reports Server (NTRS)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  6. Effects of chronic scopolamine administration on spatial working memory and hippocampal receptors related to learning.

    PubMed

    Doguc, Duygu K; Delibas, Namik; Vural, Huseyin; Altuntas, Irfan; Sutcu, Recep; Sonmez, Yonca

    2012-12-01

    Scopolamine has been used in neuropsychopharmacology as a standard drug that leads to symptoms mimicking cognitive deficits seen during the aging process in healthy humans and animals. Scopolamine is known to be a nonselective muscarinic receptor blocker, but its chronic effect on the expression of certain hippocampal receptors is not clear. The aim of the present study was to determine the effect of chronic scopolamine administration on hippocampal receptor expression and spatial working memory in two different learning tasks, the water maze and the eight-arm radial maze. Male rats (8-12 months) were trained in both tasks. Subsequently, different groups received physiological saline or 0.1, 0.8, or 2 mg/kg scopolamine hydrobromide, respectively, for 15 days. After drug administration, the rats were retested for both tasks, and hippocampal expressions of NR2A, NR2B, nAChRα7, and mAChRM1 receptors were assessed by western blotting analysis. In both tasks, the spatial working memory was decreased dose dependently in all groups compared with the control group. In terms of receptor expressions, 0.8 and 2 mg/kg scopolamine administration significantly decreased NR2A protein expression, which corroborates suggestions of an interaction between cholinergic and glutamatergic receptors in the hippocampus.

  7. Behavioral Tolerance to Anticholinergic Agents.

    DTIC Science & Technology

    negative reinforcement (avoidance of brief electric shocks). Each procedure was designed to allow within-subject determination of drug effects. In the...maintained by negative reinforcement ; c) eating of the food pellets used as positive reinforcers was suppressed by atropine, sometimes for more than a...also resulted in decreased responding. Evidence of antagonism between atropine and physostigmine was observed for behavior maintained alternatly by positive and negative reinforcement . Keywords: Tolerances(physiology);

  8. Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.

    PubMed

    Che, Magnus M; Chanda, Soma; Song, Jian; Doctor, Bhupendra P; Rezk, Peter E; Sabnekar, Praveena; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2011-07-01

    Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.

  9. [Effect of scopolamine on depression in mice].

    PubMed

    Ji, Cheng-xue; Zhang, Jian-jun

    2011-04-01

    Based on the report of previous clinical study which showed cholinergic receptor antagonist scopolamine had antidepressant activity, this study was to investigate the antidepressant activity of scopolamine and explore its effective dose in mice, and to evaluate the effect of scopolamine on the central nervous system and learning/memory ability at its antidepressant effective dose. Tail suspension test, forced swimming test, step-down passive avoidance test and open field test were used to evaluate its effects on mice. Compared with the vehicle control group, single-dose administration of scopolamine (0.1-0.4 mg x kg(-1), ip) significantly decreased the immobility time (P < 0.01 or P < 0.001) in tail suspension test, and significantly decreased the immobility time (P < 0.001) in forced swimming test, but had no effect on the step-down latency and errors in step-down passive avoidance test. Scopolamine (0.1 and 0.2 mg x kg(-1), ip) had no influence on the locomotor activity in open field test, while at dose of 0.4 mg x kg(-1) significantly increase the locomotor activity. These results showed that scopolamine produced reliable antidepressant effect at doses of 0.1 and 0.2 mg x kg(-1), without impairment on learning and memory, as well as excitory or inhibitory effect on central nervous system in mice.

  10. Dipeptide preparation Noopept prevents scopolamine-induced deficit of spatial memory in BALB/c mice.

    PubMed

    Belnik, A P; Ostrovskaya, R U; Poletaeva, I I

    2007-04-01

    The effect of original nootropic preparation Noopept on learning and long-term memory was studied with BALB/c mice. Scopolamine (1 mg/kg) impaired long-term memory trace, while Noopept (0.5 mg/kg) had no significant effect. Noopept completely prevented the development of cognitive disorders induced by scopolamine (blockade of muscarinic cholinergic receptors). Our results confirmed the presence of choline-positive effect in dipeptide piracetam analogue Noopept on retrieval of learned skill of finding a submerged platform (spatial memory). We conclude that the effectiveness of this drug should be evaluated in patients with Alzheimer's disease.

  11. Attenuating effect of bioactive coumarins from Convolvulus pluricaulis on scopolamine-induced amnesia in mice.

    PubMed

    Malik, Jai; Karan, Maninder; Vasisht, Karan

    2016-01-01

    Convolvulus pluricaulis Chois. (Convolvulaceae) has been used in Ayurveda as Medhya Rasyana (nervine tonic) to treat various mental disorders. This study was designed to isolate the bioactive compound(s) of this plant and to evaluate their effect against scopolamine-induced amnesia. Column chromatography of the chloroform and ethyl-acetate fractions led to the isolation of three coumarins identified as scopoletin, ayapanin and scopolin. All the three compounds at 2.5, 5, 10 and 15 mg/kg, p.o. were evaluated for memory-enhancing activity against scopolamine-induced amnesia using elevated plus maze and step down paradigms. Effect on acetylcholinesterase activity in mice brain was also evaluated. Scopoletin and scopolin, in both the paradigms, significantly and dose dependently attenuated the scopolamine-induced amnesic effect. Furthermore, these compounds at 10 and 15 mg/kg exhibited activity comparable to that of standard drug, donepezil. The compounds also exhibited significant acetylcholinesterase inhibitory activity.

  12. A case of pediatric age anticholinergic intoxication due to accidental Datura stramonium ingestion admitting with visual hallucination.

    PubMed

    Şanlıdağ, Burçin; Derinöz, Okşan; Yıldız, Nagehan

    2014-01-01

    Datura stramonium (DS) is a hallucinogenic plant that can produce anticholinergic toxicity because of its significant concentrations of toxic alkaloids, such as atropine, hyoscyamine, and scopolamine. DS grows in both rural and urban areas in Turkey. Clinical findings of toxicity are similar to those of atropine toxicity. DS abuse is common among adolescents because of its hallucinatory effects. However, accidental DS poisoning from contaminated food is very rare. Accidental poisonings are commonly seen among children. Children are more prone to the toxic effects of atropine; ingestion of even a small amount can cause serious central nervous system symptoms. Treatment is supportive; antidote treatment is given rarely. An eight-year-old male with accidental DS poisoning who presented to the Pediatric Emergency Department with aggression, agitation, delirium, and visual hallucinations is reported.

  13. Anticholinergic activity of 107 medications commonly used by older adults.

    PubMed

    Chew, Marci L; Mulsant, Benoit H; Pollock, Bruce G; Lehman, Mark E; Greenspan, Andrew; Mahmoud, Ramy A; Kirshner, Margaret A; Sorisio, Denise A; Bies, Robert R; Gharabawi, Georges

    2008-07-01

    The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.

  14. Pharmacokinetics of Scopolamine Intranasal Gel Formulation (INSCOP) During Antiorthostatic Bedrest

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Boyd, J. L.; Du, B.; Daniels, V.; Crady, C.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for space travelers on short and long duration space flight Oral antiemetics are not very effective in space due to poor bioavailability. Scopolamine (SCOP) is the most frequently used drug by recreational travelers V patch, tablets available on the market. Common side effects of antiemetics, in general, include drowsiness, sedation, dry mouth and reduced psychomotor performance. Severity and persistence of side effects are often dose related Side effects can be detrimental in high performance demanding settings, e.g. space flight, military.

  15. A Modified LC/MS/MS Method with Enhanced Sensitivity for the Determination of Scopolamine in Human Plasma

    NASA Technical Reports Server (NTRS)

    Wang, Zuwei; Vaksman, Zalman; Putcha, Lakshmi

    2008-01-01

    Intranasal scopolamine is a choice drug for the treatment of motion sickness during space flight because of its quick onset of action, short half-life and favorable sideeffects profile. The dose administered usually ranges between 0.1 and 0.4 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids using existing sensitive LC/MS/MS method, especially when the biological sample volumes are limited. To measure scopolamine in human plasma to facilitate pharmacokinetic evaluation of the drug, we developed a sensitive LC/MS/MS method using 96 well micro elution plates for solid phase extraction (SPE) of scopolamine in human plasma. Human plasma (100-250 micro L) were loaded onto Waters Oasis HLB 96 well micro elution plate and eluted with 50 L of organic solvent without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 3 minutes. The mobile phase for separation was 80:20 (v/v) methanol: ammonium acetate (30 mM) in water. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 right arrow 138.1 and internal standard hyoscyamine m/z = 290.2 right arrow 124.1. The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at about 1.1 and 1.7 min respectively. The linear range is 25-10000 pg/mL for scopolamine in human plasma with correlation coefficients greater than 0.99 and CV less than 0.5%. The intra-day and inter-day CVs are less than 15% for quality control samples with concentrations of 75,300, and 750 pg/mL of scopolamine in human plasma. SPE using 96 well micro elution plates allows rapid sample preparation and enhanced sensitivity for the LC

  16. A Modified LC/MS/MS Method with Enhanced Sensitivity for the Determination of Scopolamine in Human Plasma

    NASA Technical Reports Server (NTRS)

    Wang, Zuwei; Vaksman, Zalman; Putcha, Lakshmi

    2008-01-01

    Intranasal scopolamine is a choice drug for the treatment of motion sickness during space flight because of its quick onset of action, short half-life and favorable sideeffects profile. The dose administered usually ranges between 0.1 and 0.4 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids using existing sensitive LC/MS/MS method, especially when the biological sample volumes are limited. To measure scopolamine in human plasma to facilitate pharmacokinetic evaluation of the drug, we developed a sensitive LC/MS/MS method using 96 well micro elution plates for solid phase extraction (SPE) of scopolamine in human plasma. Human plasma (100-250 micro L) were loaded onto Waters Oasis HLB 96 well micro elution plate and eluted with 50 L of organic solvent without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 3 minutes. The mobile phase for separation was 80:20 (v/v) methanol: ammonium acetate (30 mM) in water. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 right arrow 138.1 and internal standard hyoscyamine m/z = 290.2 right arrow 124.1. The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at about 1.1 and 1.7 min respectively. The linear range is 25-10000 pg/mL for scopolamine in human plasma with correlation coefficients greater than 0.99 and CV less than 0.5%. The intra-day and inter-day CVs are less than 15% for quality control samples with concentrations of 75,300, and 750 pg/mL of scopolamine in human plasma. SPE using 96 well micro elution plates allows rapid sample preparation and enhanced sensitivity for the LC

  17. Anticholinergic medication use and dementia: latest evidence and clinical implications

    PubMed Central

    Gray, Shelly L.; Hanlon, Joseph T.

    2016-01-01

    Use of medications with anticholinergic activity is widespread in older adults. Several studies have highlighted that anticholinergic use may be associated with an increased risk of dementia. The objective of this narrative review is to describe and evaluate studies of anticholinergic medication use and dementia and provide practical suggestions for avoiding use of these medications in older adults. A comprehensive review of the literature, citations from recent reviews and the author’s personal files was conducted. Four studies were found that evaluated anticholinergic use and dementia as the primary outcome. Three studies focused on overall anticholinergic medication use and reported a statistically significantly increased risk of Alzheimer’s disease or dementia. In one study, dementia risk was primarily found with higher cumulative doses; people using anticholinergic medications at the minimum effective dose recommended for older adults for at least 3 years were at highest risk. In contrast, a study conducted in nursing-home residents with depression did not find that paroxetine [a highly anticholinergic selective serotonin reuptake inhibitor antidepressant, (SSRI)] increased risk for dementia compared with other SSRIs (without anticholinergic activity). Further study is needed to understand the mechanism by which anticholinergic medications may increase risk. In conclusion, there is evidence from three observational studies suggesting that anticholinergic medications may increase dementia risk. Given this potential risk and the myriad of other well-known adverse effects (i.e. constipation, blurred vision, urinary retention, and delirium) associated with anticholinergic medications, it is prudent for prescribers and older adults to minimize use of these medications and consider alternatives when possible. PMID:27695623

  18. Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.

    PubMed

    Spence, Michele M; Karim, Fatima A; Lee, Eric A; Hui, Rita L; Gibbs, Nancy E

    2015-06-01

    To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults. Retrospective case-control study. Integrated healthcare system. Healthcare system members aged 65 and older (N = 260,010; 54,152 cases, 205,858 controls). Cases were identified as individuals with an injury resulting in a hospitalization, emergency department, or urgent care visit (index date) from January 2009 through December 2010. Cases and controls were matched in a 1:4 ratio based on age and sex. GI antispasmodic and anticholinergic current and past exposure for cases and controls was evaluated. Individuals were classified as current users if the days' supply of the GI prescription overlapped the index date and past users if the days' supply ended more than 60 days before the index date. Duration of use for current users was analyzed for short- and long-term use. Conditional logistic regression produced adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Of the total population, 1,068 (0.4%) had current exposure to a GI antispasmodic or anticholinergic (302 (0.6%) cases, 766 (0.4%) controls). Current users had a small but significantly greater risk of injury than nonusers (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Past use was not significantly different from no use. Short-term users had a significantly greater risk of injury (OR = 1.31, 95% CI = 1.01-1.70, P = .04) than nonusers. Long-term use was associated with greater risk, but the difference was not statistically significant. Older adults using GI antispasmodic and anticholinergic drugs have greater risk of injury. These findings support recommendations to limit the prescribing of GI antispasmodics and anticholinergics in elderly adults. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  19. Jimson weed toxicity: management of anticholinergic plant ingestion.

    PubMed

    Vanderhoff, B T; Mosser, K H

    1992-08-01

    Jimson weed is a hallucinogenic plant that is common in rural areas. Consumption of any part of the plant can result in severe anticholinergic toxicity. The clinical presentation of jimson weed toxicity is similar to that seen in cases of atropine poisoning. Treatment is aimed at removing plant material from the gastrointestinal tract, keeping the patient safe and reversing severe anticholinergic sequelae.

  20. Antiparkinson drugs used as prophylactics for nerve agents: studies of cognitive side effects in rats.

    PubMed

    Myhrer, Trond; Enger, Siri; Aas, Pål

    2008-06-01

    Antiparkinson agents possess excellent anticonvulsant properties against nerve agent-induced seizures by exerting both cholinergic and glutamatergic antagonisms. It is important, however, that drugs used as prophylactics not by themselves cause impairment of cognitive capability. The purpose of the present study was to make a comparative assessment of potential cognitive effects of benactyzine (0.3 mg/kg), biperiden (0.11 mg/kg), caramiphen (10 mg/kg), procyclidine (3 mg/kg), and trihexyphenidyl (0.12 mg/kg) separately and each in combination with physostigmine (0.1 mg/kg). The results showed that benactyzine, caramiphen, and trihexyphenidyl reduced rats' innate preference for novelty, whereas biperiden and procyclidine did not. When benactyzine, caramiphen, and trihexyphenidyl were combined with physostigmine the cognitive impairment disappeared. This counteracting effect, however, caused changes in locomotor and rearing activities not seen by each drug alone. Acetylcholinesterase inhibitors and anticholinergics used as prophylactics can offset each other, but exceptions are observed in a previous study when a very potent anticholinergic (scopolamine) or a high dose of procyclidine still results in cognitive deficits in spite of coadministration with physostigmine. Among the present drugs tested, procyclidine appears to be a robust anticonvulsant with few cognitive side effects.

  1. Effects of clonidine and scopolamine on multiple target detection in rapid serial visual presentation.

    PubMed

    Brown, Stephen B R E; Slagter, Heleen A; van Noorden, Martijn S; Giltay, Erik J; van der Wee, Nic J A; Nieuwenhuis, Sander

    2016-01-01

    The specific role of neuromodulator systems in regulating rapid fluctuations of attention is still poorly understood. In this study, we examined the effects of clonidine and scopolamine on multiple target detection in a rapid serial visual presentation task to assess the role of the central noradrenergic and cholinergic systems in temporal attention. Eighteen healthy volunteers took part in a crossover double-dummy study in which they received clonidine (150/175 μg), scopolamine (1.2 mg), and placebo by mouth in counterbalanced order. A dual-target attentional blink task was administered at 120 min after scopolamine intake and 180 min after clonidine intake. The electroencephalogram was measured during task performance. Clonidine and scopolamine both impaired detection of the first target (T1). For clonidine, this impairment was accompanied by decreased amplitudes of the P2 and P3 components of the event-related potential. The drugs did not impair second-target (T2) detection, except if T2 was presented immediately after T1. The attentional blink for T2 was not affected, in line with a previous study that found no effect of clonidine on the attentional blink. These and other results suggest that clonidine and scopolamine may impair temporal attention through a decrease in tonic alertness and that this decrease in alertness can be temporarily compensated by a phasic alerting response to a salient stimulus. The comparable behavioral effects of clonidine and scopolamine are consistent with animal studies indicating close interactions between the noradrenergic and cholinergic neuromodulator systems.

  2. The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.

    PubMed

    Lochner, Martin; Thompson, Andrew J

    2016-09-01

    Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects.

  3. Scopolamine impairs memory recall in Octopus vulgaris.

    PubMed

    Fiorito, G; Agnisola, C; d'Addio, M; Valanzano, A; Calamandrei, G

    1998-09-04

    The involvement of the central cholinergic system in predatory performance, and on the recall of individual and observational memory in Octopus vulgaris was studied by treating the animals with the muscarinic antagonist scopolamine (2 mg/kg). The absence of the effects of the injection of scopolamine on blood circulation was also checked. Scopolamine did not affect the ability of octopuses to prey on live crabs. However, it interfered significantly with memory recall. In fact, the ability to solve the jar problem was impaired within the first hour after injection (short-term effects) and was only partially recovered after 24 h (long-term). Moreover, both individual and observational learning of a visual discrimination were significantly reduced at the short- and long-term testing. These results support a role of the cholinergic system in the processes of memory recall of O. vulgaris.

  4. The effects of amphetamine and scopolamine on adjunctive drinking and wheel-running in rats.

    PubMed

    Williams, J L; White, J M

    1984-01-01

    Two groups of rats were exposed to a fixed-interval 90 s schedule of food reinforcement. One group had access to a drinking tube containing water and the second had access to a running wheel. Amphetamine (0.3-10.0 mg/kg) and scopolamine (0.1-3.0 mg/kg) were assessed for their effects on lever-pressing, adjunctive drinking and adjunctive wheel-running. Low to moderate doses of amphetamine increased overall rates of lever-pressing, whereas the highest dose decreased them. Scopolamine decreased overall lever-pressing rates in a dose-dependent manner. Both drugs changed the within-interval pattern of lever-pressing from one of increasing probability through the interval to almost constant probability throughout. Overall rates of adjunctive drinking and adjunctive wheel-running were decreased by amphetamine and scopolamine. Amphetamine failed to alter the within-interval patterns of either drinking or wheel-running in any substantial manner. The effect of scopolamine was to make the probabilities of each adjunctive behaviour more even through the interval. Although the two drugs had different actions, there was little difference in the way drinking and wheel-running were affected by each.

  5. No influence of scopolamine hydrobromide on odor detection performance of rats.

    PubMed

    Doty, Richard L; Bagla, Ritu; Misra, Robert; Mueller, Eric; Kerr, Kara-Lynne

    2003-11-01

    Despite speculation that the muscarinic cholinergic antagonist, scopolamine, may influence the olfactory sensitivity of rats, there have been no definitive studies on this point to date. In this study, we examined the influence of a range of doses of scopolamine hydrobromine (namely, 0.10, 0.125, 0.15 and 0.20 mg/kg i.p.) on the odor detection performance of 15 adult male Long-Evans rats to ethyl acetate. Air-dilution olfactometry and a go/no-go operant signal detection task were employed. The drug conditions and a saline control were administered to each animal in an order counterbalanced by Latin squares, with 2 day intervals interspersed between tests. Scopolamine had no significant influence on odor detection performance per se, as measured by percent correct S+ and S- responses and a non-parametric signal detection measure of sensitivity. This is in contrast to the relatively large effects previously observed in the same test paradigm for such drugs as the D-1 agonist SKF 38393 and the D-2 agonist quinpirole. These data suggest that scopolamine has no meaningful influence on a well-practiced odor detection task.

  6. Refractory overactive bladder: Beyond oral anticholinergic therapy

    PubMed Central

    Glinski, Ronald W.; Siegel, Steven

    2007-01-01

    Objectives: In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments. Materials and Methods: A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options. Results: In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted. Conclusion: The vast majority of OAB patients can be managed successfully by behavioral options with or without

  7. Comparing anticholinergic persistence and adherence profiles in overactive bladder patients based on gender, obesity, and major anticholinergic agents.

    PubMed

    Lua, Lannah L; Pathak, Prathamesh; Dandolu, Vani

    2017-05-03

    Overactive bladder (OAB) is highly prevalent particularly among obese patients and significantly impacts quality of life. Anticholinergics are the first-line treatment. The effect of obesity on medication compliance has not been studied. Our study evaluated gender- and obesity-specific adherence and persistence of anticholinergic medications in OAB. We also compared adherence and persistence on solifenacin to oxybutynin, tolterodine, and all anticholinergics combined. Truven Marketscan Commercial Claims and Encounter database from 2005 to 2013 was used. OAB patients aged 18-65 continuously enrolled for ≥12 months pre- and post-index were identified. Adherence was assessed by medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as number of days from anticholinergic initiation to discontinuation, switch, or end of study. Statistical analyses were performed using SAS 9.3. Among 122 641 OAB patients, most common comorbidities were hypertension, depression, and diabetes; patients with these conditions were more compliant. Obese patients were 7% less likely to adhere and 6% more likely to become non-persistent on anticholinergics compared to non-obese. Males were 20% more likely to adhere to anticholinergics compared to females. Oxybutynin, solifenacin, and tolterodine were the most common anticholinergics. Solifenacin demonstrated higher adherence and persistence compared to all anticholinergics combined. The proportion of patients still on solifenacin at 1 year was 17.11%, compared to 12.64% for all anticholinergics combined. Men are more likely to be adherent to anticholinergics than women. Obese patients are less likely to be compliant to medications, possibly related to severity of symptoms. Solifenacin had the highest rates of patient compliance. © 2017 Wiley Periodicals, Inc.

  8. Use of anticholinergic bronchodilation in children.

    PubMed

    Rubin, B K; Albers, G M

    1996-01-29

    Ipratropium bromide is a quaternary ammonium anticholinergic bronchodilator with minimal systemic absorption across the blood-airway barrier. Ipratropium bromide has become primary therapy for the treatment of adults with chronic bronchitis, but its use in children has been limited. Ipratropium bromide can be safely used in the management of acute bronchiolitis, recognizing that most infants do not appear to respond to any bronchodilator medication. When used with a beta-agonist bronchodilator for the therapy of acute childhood asthma, ipratropium bromide appears to provide bronchodilation beyond that achieved by either agent used alone. There are insufficient published data to determine the appropriate use if ipratropium bromide in infants with bronchopulmonary dysplasia, although many of those symptomatic after the age of 6 months seem to benefit from either ipratropium bromide or beta-agonists. As ipratropium bromide has no intrinsic anti-inflammatory properties, its role in the chronic therapy of asthma and related disorders is still unclear.

  9. Dementia and lower urinary dysfunction: with a reference to anticholinergic use in elderly population.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Yamanishi, Tomonori; Kishi, Masahiko

    2008-09-01

    Urinary incontinence is common in patients with dementia, and is more prevalent in demented than in non-demented older individuals. Neurogenic incontinence is common in multiple cerebral infarction and dementia with Lewy bodies, and in both diseases walking difficulty and falls are common. In contrast, functional incontinence is common in Alzheimer's disease due to cognitive disability and decreased motivation. Central cholinergic stimulation is the mainstay in the treatment of cognitive decline. In contrast, to date, the use of anticholinergic medications for detrusor overactivity in the elderly is still under consideration, since anticholinergic drugs may lead to undesirable events particularly in the central nervous system, although many studies have used severely demented cases. In the future, studies seeking treatment regimens for an elderly individual with both dementia and urinary dysfunction are warranted.

  10. Reversal of scopolamine-induced disruption of prepulse inhibition by clozapine in mice

    PubMed Central

    Singer, Philipp; Yee, Benjamin K.

    2012-01-01

    Prepulse inhibition (PPI) of the acoustic startle reflex refers to the reduction of the startle response to an intense acoustic pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus and provides a cross-species measure of sensory-motor gating. PPI is typically impaired in schizophrenia patients, and a similar impairment can be induced in rats by systemic scopolamine, a muscarinic cholinergic receptor antagonist that can evoke a range of cognitive and psychotic symptoms in healthy humans that are commonly referred to as the “anti-muscarinic syndrome” resembling some clinical features of schizophrenia. Scopolamine-induced PPI disruption has therefore been proposed as an anti-muscarinic animal model of schizophrenia, but parallel investigations in the mouse remain scant and the outcomes are mixed and often confounded by an elevation of startle reactivity. Here, we distinguished the PPI-disruptive and the confounding startle-enhancing effects of scopolamine (1 and 10 mg/kg, i.p.) in C57BL/6 wild-type mice by showing that the latter partly stemmed from a shift in spontaneous baseline reactivity. With appropriate correction for between-group differences in startle reactivity, we went on to confirm that the PPI-disruptive effect of scopolamine could be nullified by clozapine pre-treatment (1.5 mg/kg, i.p.) in a dose-dependent manner. This is the first demonstration that scopolamine-induced PPI disruption is sensitive to atypical antipsychotic drugs. In concert with previous data showing its sensitivity to haloperidol the present finding supports the predictive validity of the anti-muscarinic PPI disruption model for both typical and atypical antipsychotic drug action. PMID:22210488

  11. Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine

    PubMed Central

    Wohleb, Eric S.; Gerhard, Danielle; Thomas, Alex; Duman, Ronald S.

    2017-01-01

    Major depressive disorder (MDD) is a prevalent neuropsychiatric disease that causes profound social and economic burdens. The impact of MDD is compounded by the limited therapeutic efficacy and delay of weeks to months of currently available medications. These issues highlight the need for more efficacious and faster-acting treatments to alleviate the burdens of MDD. Recent breakthroughs demonstrate that certain drugs, including ketamine and scopolamine, produce rapid and long-lasting antidepressant effects in MDD patients. Moreover, preclinical work has shown that the antidepressant actions of ketamine and scopolamine in rodent models are caused by an increase of extracellular glutamate, elevated BDNF, activation of the mammalian target of rapamycin complex 1 (mTORC1) cascade, and increased number and function of spine synapses in the prefrontal cortex (PFC). Here we review studies showing that both ketamine and scopolamine elicit rapid antidepressant effects through converging molecular and cellular mechanisms in the PFC. In addition, we discuss evidence that selective antagonists of NMDA and muscarinic acetylcholine (mACh) receptor subtypes (i.e., NR2B and M1-AChR) in the PFC produce comparable antidepressant responses. Furthermore, we discuss evidence that ketamine and scopolamine antagonize inhibitory interneurons in the PFC leading to disinhibition of pyramidal neurons and increased extracellular glutamate that promotes the rapid antidepressant responses to these agents. Collectively, these studies indicate that specific NMDA and mACh receptor subtypes on GABAergic interneurons are promising targets for novel rapid-acting antidepressant therapies. PMID:26955968

  12. Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine.

    PubMed

    Wohleb, Eric S; Gerhard, Danielle; Thomas, Alex; Duman, Ronald S

    2017-01-01

    Major depressive disorder (MDD) is a prevalent neuropsychiatric disease that causes profound social and economic burdens. The impact of MDD is compounded by the limited therapeutic efficacy and delay of weeks to months of currently available medications. These issues highlight the need for more efficacious and faster-acting treatments to alleviate the burdens of MDD. Recent breakthroughs demonstrate that certain drugs, including ketamine and scopolamine, produce rapid and long-lasting antidepressant effects in MDD patients. Moreover, preclinical work has shown that the antidepressant actions of ketamine and scopolamine in rodent models are caused by an increase of extracellular glutamate, elevated BDNF, activation of the mammalian target of rapamycin complex 1 (mTORC1) cascade, and increased number and function of spine synapses in the prefrontal cortex (PFC). Here we review studies showing that both ketamine and scopolamine elicit rapid antidepressant effects through converging molecular and cellular mechanisms in the PFC. In addition, we discuss evidence that selective antagonists of NMDA and muscarinic acetylcholine (mACh) receptor subtypes (i.e., NR2B and M1-AChR) in the PFC produce comparable antidepressant responses. Furthermore, we discuss evidence that ketamine and scopolamine antagonize inhibitory interneurons in the PFC leading to disinhibition of pyramidal neurons and increased extracellular glutamate that promotes the rapid antidepressant responses to these agents. Collectively, these studies indicate that specific NMDA and mACh receptor subtypes on GABAergic interneurons are promising targets for novel rapid-acting antidepressant therapies.

  13. Galantamine reverses scopolamine-induced behavioral alterations in Dugesia tigrina.

    PubMed

    Ramakrishnan, Latha; Amatya, Christina; DeSaer, Cassie J; Dalhoff, Zachary; Eggerichs, Michael R

    2014-09-01

    In planaria (Dugesia tigrina), scopolamine, a nonselective muscarinic receptor antagonist, induced distinct behaviors of attenuated motility and C-like hyperactivity. Planarian locomotor velocity (pLMV) displayed a dose-dependent negative correlation with scopolamine concentrations from 0.001 to 1.0 mM, and a further increase in scopolamine concentration to 2.25 mM did not further decrease pLMV. Planarian hyperactivity counts was dose-dependently increased following pretreatment with scopolamine concentrations from 0.001 to 0.5 mM and then decreased for scopolamine concentrations ≥ 1 mM. Planarian learning and memory investigated using classical Pavlovian conditioning experiments demonstrated that scopolamine (1 mM) negatively influenced associative learning indicated by a significant decrease in % positive behaviors from 86 % (control) to 14 % (1 mM scopolamine) and similarly altered memory retention, which is indicated by a decrease in % positive behaviors from 69 % (control) to 27 % (1 mM scopolamine). Galantamine demonstrated a complex behavior in planarian motility experiments since co-application of low concentrations of galantamine (0.001 and 0.01 mM) protected planaria against 1 mM scopolamine-induced motility impairments; however, pLMV was significantly decreased when planaria were tested in the presence of 0.1 mM galantamine alone. Effects of co-treatment of scopolamine and galantamine on memory retention in planaria via classical Pavlovian conditioning experiments showed that galantamine (0.01 mM) partially reversed scopolamine (1 mM)-induced memory deficits in planaria as the % positive behaviors increased from 27 to 63 %. The results demonstrate, for the first time in planaria, scopolamine's effects in causing learning and memory impairments and galantamine's ability in reversing scopolamine-induced memory impairments.

  14. Effect of pregabalin on fear-based conditioned avoidance learning and spatial learning in a mouse model of scopolamine-induced amnesia.

    PubMed

    Sałat, Kinga; Podkowa, Adrian; Malikowska, Natalia; Trajer, Jędrzej

    2017-03-01

    Cognitive deficits are one of the frequent symptoms accompanying epilepsy or its treatment. In this study, the effect on cognition of intraperitoneally administered antiepileptic drug, pregabalin (10 mg/kg), was investigated in scopolamine-induced memory-impaired mice in the passive avoidance task and Morris water maze task. The effect of scopolamine and pregabalin on animals' locomotor activity was also studied. In the retention phase of the passive avoidance task, pregabalin reversed memory deficits induced by scopolamine (p < 0.05). During the acquisition phase of the Morris water maze pregabalin-treated memory-impaired mice performed the test with longer escape latencies than the vehicle-treated mice (significant at p < 0.05 on Day 5, and at p < 0.001 on Day 6). There were no differences in this parameter between the scopolamine-treated control group and pregabalin-treated memory-impaired mice, which indicated that pregabalin had no influence on spatial learning in this task. During the probe trial a significant difference (p < 0.05) was observed in terms of the mean number of target crossings between vehicle-treated mice and pregabalin-treated memory-impaired mice but there was no difference between the scopolamine-treated control group and mice treated with pregabalin + scopolamine. Pregabalin did not influence locomotor activity increased by scopolamine. In passive avoidance task, pregabalin reversed learning deficits induced by scopolamine. In the Morris water maze, pregabalin did not influence spatial learning deficits induced by scopolamine. These results are relevant for epileptic patients treated with pregabalin and those who use it for other therapeutic indications (anxiety, pain).

  15. Saturation solubility of nicotine, scopolamine and paracetamol in model stratum corneum lipid matrices.

    PubMed

    Mundstock, Anne; Lee, Geoffrey

    2014-10-01

    The saturation solubilities of nicotine and scopolamine bases as well as acidic paracetamol were measured in two different model stratum corneum lipid matrices. Light microscopy visualized the presence of drug above its solubility either as droplets or crystalline particles. Neither wide-angle X-ray diffraction nor DSC detected the drugs. The saturation solubilities of the nicotine and scopolamine bases are 3-5% w/w and 5-10% w/w respectively. Paracetamol strongly disrupts the lamellar phase formed by the lipids and could be dissolved to >20% w/w. Based on these results the saturation solubilities of nicotine and scopolamine in an intact stratum corneum membrane are estimated to be up to 17.5 μg and 35 μg drug per milligrams of stratum corneum membrane respectively. These concentrations are well above values obtained by tape stripping of intact stratum corneum during a permeation experiment. The drug's saturation solubility in the stratum corneum's lipid phase is therefore unlikely to be rate-limiting for permeation of these two drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

    NASA Technical Reports Server (NTRS)

    Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

    2007-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training

  17. Blood-brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder.

    PubMed

    Chancellor, Michael B; Staskin, David R; Kay, Gary G; Sandage, Bobby W; Oefelein, Michael G; Tsao, Jack W

    2012-04-01

    Overactive bladder (OAB) is a common condition, particularly in the elderly. Anticholinergic agents are the mainstay of pharmacological treatment of OAB; however, many anticholinergics can cross the blood-brain barrier (BBB) and may cause central nervous system (CNS) effects, including cognitive deficits, which can be especially detrimental in older patients. Many anticholinergics have the potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding in the brain. Of note, permeability of the BBB increases with age and can also be affected by trauma, stress, and some diseases and medications. Passive crossing of a molecule across the BBB into the brain is dependent upon its physicochemical properties. Molecular characteristics that hinder passive BBB penetration include a large molecular size, positive or negative ionic charge at physiological pH, and a hydrophilic structure. Active transport across the BBB is dependent upon protein-mediated transporter systems, such as that of permeability-glycoprotein (P-gp), which occurs only for P-gp substrates, such as trospium chloride, darifenacin and fesoterodine. Reliance on active transport can be problematic since genetic polymorphisms of P-gp exist, and many commonly used drugs and even some foods are P-gp inhibitors or are substrates themselves and, due to competition, can reduce the amount of the drug that is actively transported out of the CNS. Therefore, for drugs that are preferred not to cross into the CNS, such as potent anticholinergics intended for the bladder, it is optimal to have minimal passive crossing of the BBB, although it may also be beneficial for the drug to be a substrate for an active efflux transport system. Anticholinergics demonstrate different propensities to cross the BBB. Darifenacin, fesoterodine and trospium chloride are substrates for P-gp and, therefore, are actively transported away from the brain. In addition, trospium chloride has not been detected in cerebrospinal

  18. Dexmedetomidine Infusion to Control Agitation due to Anticholinergic Toxidromes in Adolescents, a Case Series

    PubMed Central

    Lin, Ada; Tobias, Joseph D.

    2015-01-01

    Dexmedetomidine is an α2-adrenergic agonist approved by the US Food and Drug Administration for the sedation of adults who are intubated on mechanical ventilation and in non-intubated adults who are undergoing surgical procedures. However, it has also recently become a commonly used sedative agent in varied clinical settings for the pediatric patient as well. We present the use of dexmedetomidine for sedation in a unique clinical scenario, the severely agitated and combative patient following the intentional misuse of anticholinergic drugs. Its applications in this situation are discussed, and previous reports in the literature are reviewed. PMID:26380573

  19. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    NASA Technical Reports Server (NTRS)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  20. Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats.

    PubMed

    Rahmati, Batool; Kiasalari, Zahra; Roghani, Mehrdad; Khalili, Mohsen; Ansari, Fariba

    2017-12-01

    Anxiety and depression are common in Alzheimer's disease (AD). Despite some evidence, it is difficult to confirm Lavandula officinalis Chaix ex Vill (Lamiaceae) as an anxiolytic and antidepressant drug. The effects of L. officinalis extract were studied in scopolamine-induced memory impairment, anxiety and depression-like behaviour. Male NMRI rats were divided into control, scopolamine alone-treated group received scopolamine (0.1 mg/kg) intraperitoneally (i.p.), daily and 30 min prior to performing behavioural testing on test day, for 12 continuous days and extract pretreated groups received aerial parts hydro alcoholic extract (i.p.) (100, 200 and 400 mg/kg), 30 min before each scopolamine injection. Memory impairment was assessed by Y-maze task, while, elevated plus maze and forced swimming test were used to measure anxiolytic and antidepressive-like activity. Spontaneous alternation percentage in Y maze is reduced by scopolamine (36.42 ± 2.60) (p ≤ 0.001), whereas lavender (200 and 400 mg/kg) enhanced it (83.12 ± 5.20 and 95 ± 11.08, respectively) (p ≤ 0.05). Also, lavender pretreatment in 200 and 400 mg/kg enhanced time spent on the open arms (15.4 ± 3.37 and 32.1 ± 3.46, respectively) (p ≤ 0.001). On the contrary, while immobility time was enhanced by scopolamine (296 ± 4.70), 100, 200 and 400 mg/kg lavender reduced it (193.88 ± 22.42, 73.3 ± 8.25 and 35.2 ± 4.22, respectively) in a dose-dependent manner (p ≤ 0.001). Lavender extracts improved scopolamine-induced memory impairment and also reduced anxiety and depression-like behaviour in a dose-dependent manner.

  1. Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model.

    PubMed

    Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Han, Jong-Min; Lee, Sam-Keun; Kim, Dong-Woon; Saravanakumar, Arthanari; Son, Chang-Gue

    2015-05-14

    We evaluated the neuropharmacological effects of 30% ethanolic pine needle extract (PNE) on memory impairment caused by scopolamine injection in mice hippocampus. Mice were orally pretreated with PNE (25, 50, and 100 mg/kg) or tacrine (10 mg/kg) for 7 days, and scopolamine (2 mg/kg) was injected intraperitoneally, 30 min before the Morris water maze task on first day. To evaluate memory function, the Morris water maze task was performed for 5 days consecutively. Scopolamine increased the escape latency and cumulative path-length but decreases the time spent in target quadrant, which were ameliorated by pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase activity, neurogenesis and their connecting pathway were abnormally altered by scopolamine in hippocampus and/or sera, while those alterations were recovered by pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased the proliferating cells and immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained cells. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) in both protein and gene were facilitated by PNE pretreatment. These findings suggest that PNE could be a potent neuropharmacological drug against amnesia, and its possible mechanism might be modulating cholinergic activity via CREB-BDNF pathway.

  2. Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model

    PubMed Central

    Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Han, Jong-Min; Lee, Sam-Keun; Kim, Dong-Woon; Saravanakumar, Arthanari; Son, Chang-Gue

    2015-01-01

    We evaluated the neuropharmacological effects of 30% ethanolic pine needle extract (PNE) on memory impairment caused by scopolamine injection in mice hippocampus. Mice were orally pretreated with PNE (25, 50, and 100 mg/kg) or tacrine (10 mg/kg) for 7 days, and scopolamine (2 mg/kg) was injected intraperitoneally, 30 min before the Morris water maze task on first day. To evaluate memory function, the Morris water maze task was performed for 5 days consecutively. Scopolamine increased the escape latency and cumulative path-length but decreases the time spent in target quadrant, which were ameliorated by pretreatment with PNE. Oxidant-antioxidant balance, acetylcholinesterase activity, neurogenesis and their connecting pathway were abnormally altered by scopolamine in hippocampus and/or sera, while those alterations were recovered by pretreatment with PNE. As lipid peroxidation, 4HNE-positive stained cells were ameliorated in hippocampus pretreated with PNE. Pretreatment with PNE increased the proliferating cells and immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by ki67- and DCX-positive stained cells. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) in both protein and gene were facilitated by PNE pretreatment. These findings suggest that PNE could be a potent neuropharmacological drug against amnesia, and its possible mechanism might be modulating cholinergic activity via CREB-BDNF pathway. PMID:25974329

  3. Effects of transdermal scopolamine, alone or in combination with cimetidine, on total 24 hour gastric acid secretion in patients with duodenal ulcer.

    PubMed Central

    Richardson, C T; Feldman, M

    1986-01-01

    Transdermal scopolamine is an antimuscarinic preparation approved for use in the United States for prevention of motion sickness. A recent study using this drug (0.5 mg/patch) suggested that enough scopolamine was absorbed through the skin to reduce basal gastric acid secretion in patients with duodenal ulcer. We have compared the effect of transdermal scopolamine and oral cimetidine (400 mg twice daily) in seven men with chronic duodenal ulcer, both alone and in combination, on acid secretion throughout an entire 24 hour period in a placebo-controlled, randomised, double blinded cross over study. The effect of these drugs on basal, interprandial, and nocturnal gastric juice volume and hydrogen ion concentration also was measured. Transdermal scopolamine had no significant effect on mean 24 hour acid secretion (placebo, 409.4 mmol/day; scopolamine, 364.0 mmol/day) nor did it have a significant effect on gastric juice volume or hydrogen ion concentration. The combination of transdermal scopolamine plus cimetidine was not more effective than cimetidine alone in reducing total 24 hour acid secretion (mean, 231.8 versus 235.3 mmol/day) nor in reducing gastric juice volume or hydrogen ion concentration. PMID:3804025

  4. Combined Scopolamine and Ethanol Treatment Results in a Locomotor Stimulant Response Suggestive of Synergism That is Not Blocked by Dopamine Receptor Antagonists

    PubMed Central

    Scibelli, Angela C.; Phillips, Tamara J.

    2010-01-01

    Background Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol’s stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. Methods Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. Results FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. Conclusions These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically

  5. Effect of anticholinergic use for the treatment of overactive bladder on cognitive function in postmenopausal women.

    PubMed

    Geller, Elizabeth J; Crane, Andrea K; Wells, Ellen C; Robinson, Barbara L; Jannelli, Mary L; Khandelwal, Christine M; Connolly, Annamarie; Parnell, Brent A; Matthews, Catherine A; Dumond, Julie B; Busby-Whitehead, Jan

    2012-10-01

    Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs, including cognitive changes. The objective of this study was to investigate the effect of an anticholinergic medication, trospium chloride, on cognitive function in postmenopausal women being treated for OAB. This was a prospective cohort study conducted at a urogynaecology clinic at one academic medical centre from January to December 2010, with 12-week follow-up after medication initiation. Women aged 55 years or older seeking treatment for OAB and opting for anticholinergic therapy were recruited. Baseline cognitive function was assessed via the Hopkins Verbal Learning Test-Revised Form (HVLT-R) [and its five subscales], the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality-of-life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance. The main outcome measure was change in HVLT-R score at Week 4 after medication initiation, compared with baseline (pre-medication) score. Of 50 women enrolled, 35 completed the assessment. The average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p = 0.037), HVLT-R Delayed Recognition subscale (p = 0.011) and HVLT-R Recognition Bias subscale (p = 0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p = 0.029). All HVLT-R scores normalized by Week 4. OMC

  6. Rationale for the Use of Anticholinergic Agents in Overactive Bladder With Regard to Central Nervous System and Cardiovascular System Side Effects

    PubMed Central

    Onal, Bulent

    2013-01-01

    Purpose Central nervous system (CNS) and cardiovascular system (CVS) side effects of anticholinergic agents used to treat overactive bladder (OAB) are underreported. Hence, this review aimed to focus on the mechanisms of CNS and CVS side effects of anticholinergic drugs used in OAB treatment, which may help urologists in planning the rationale for OAB treatment. Materials and Methods PubMed/MEDLINE was searched for the key words "OAB," "anticholinergics," "muscarinic receptor selectivity," "blood-brain barrier," "CNS," and "CVS side effects." Additional relevant literature was determined by examining the reference lists of articles identified through the search. Results CNS and CVS side effects, pharmacodynamic and pharmacokinetic properties, the metabolism of these drugs, and the clinical implications for their use in OAB are presented and discussed in this review. Conclusions Trospium, 5-hydroxymethyl tolterodine, darifenacin, and solifenacin seem to have favorable pharmacodynamic and pharmacokinetic properties with regard to CNS side effects, whereas the pharmacodynamic features of darifenacin, solifenacin, and oxybutynin appear to have an advantage over the other anticholinergic agents (tolterodine, fesoterodine, propiverine, and trospium) with regard to CVS side effects. To determine the real-life situation, head-to-head studies focusing especially on CNS and CVS side effects of OAB anticholinergic agents are urgently needed. PMID:24363860

  7. Pharmacokinetics of Scopolamine Intranasal Gel Formulation (INSCOP) During Antiorthostatic Bedrest

    NASA Technical Reports Server (NTRS)

    Putcha, L.; Du, B.; Daniels, V.

    2010-01-01

    Space Motion Sickness (SMS) is experienced during early flight days of space missions and on reduced gravity simulation flights which require treatment with medications. Oral administration of scopolamine tablets is still a common practice to prevent SMS symptoms. Bioavailability of medications taken by mouth for SMS is often low and variable. Intranasal (IN) administration of medications has been reported to achieve higher and more reliable bioavailability than from an equivalent oral dose. In this FDA reviewed phase II clinical trial, we evaluated pharmacokinetics of an investigative new drug formulation, INSCOP during ambulatory (AMB) and antiorthostatic bedrest (HBR), a ground-based microgravity analog. Twelve subjects including 6 males and 6 females received 0.2 and 0.4 mg doses of INSCOP on separate days during AMB and ABR in a randomized, double blind cross over experimental design. Blood samples were collected at regular time intervals for 24 h post dose and analyzed for free scopolamine concentrations by an LC-MS-MS method. Pharmacokinetic parameters were calculated using concentration versus time data and compared between AMB and ABR conditions. Results indicated that maximum concentration and relative bioavailability increased marginally during ABR compared to AMB; differences in PK parameters between AMB and ABR were greater with 0.2 mg than with 0.4 mg dose. Gender specific differences in PK parameters was observed both during AMB and ABR with differences higher in females between the two conditions than in males. A significant observation is that while gender differences in PK appear to exist, the differences in primary PK parameters between AMB and ABR after IN administration, unlike oral administration, are minimal and may not be clinically significant for both genders.

  8. Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig.

    PubMed

    Shaoul, Esther; Ayalon, Ari; Tal, Yossi; Lotan, Tamar

    2012-01-01

    Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts), comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with T(max) of 30 minutes and C(max) 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery.

  9. Transdermal Delivery of Scopolamine by Natural Submicron Injectors: In-Vivo Study in Pig

    PubMed Central

    Shaoul, Esther; Ayalon, Ari; Tal, Yossi; Lotan, Tamar

    2012-01-01

    Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts), comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with Tmax of 30 minutes and Cmax 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery. PMID:22363770

  10. Bad trip due to anticholinergic effect of cannabis.

    PubMed

    Mangot, Ajish G

    2013-01-01

    Cannabis in its various forms has been known since time immemorial, the use of which has been rising steadily in India. 'Bad trips' have been documented after cannabis use, manifestations ranging from vague anxiety and fear to profoundly disturbing states of terror and psychosis. Cannabis is known to affect various neurotransmitters, but 'bad trip' due to its anticholinergic effect has never been described in literature to the best of author's knowledge. Hereby, the author describes a case of a young adult male experiencing profound anticholinergic effects after being exposed for the first time in his life to bhang, a local oral preparation of cannabis.

  11. Methyl jasmonate increases the tropane alkaloid scopolamine and reduces natural herbivory in Brugmansia suaveolens: is scopolamine responsible for plant resistance?

    PubMed

    Arab, A; Alves, M N; Sartoratto, A; Ogasawara, D C; Trigo, J R

    2012-02-01

    The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted plants which were left 10 days in the field. MJ-treated plants increased their scopolamine concentration in leaves and herbivory decreased. These findings suggest a cause-effect relationship. However, experiments in laboratory showed that scopolamine affect differently the performance of the specialist larvae of the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that sequester this TA from B. suaveolens leaves was not negatively affected, but the generalist was. Therefore, scopolamine probably acts only against insects that are not adapted to TAs. Other compounds that are MJ elicited may also play a role in plant resistance against herbivory by generalist and specialist insects, and deserve future investigations.

  12. [Preparation of scopolamine hydrobromide nanoparticles-in-microsphere system].

    PubMed

    Lü, Wei-ling; Hu, Jin-hong; Zhu, Quan-gang; Li, Feng-qian

    2010-07-01

    This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.

  13. Intranasal scopolamine affects the semicircular canals centrally and peripherally.

    PubMed

    Weerts, Aurélie P; Putcha, Lakshmi; Hoag, Stephen W; Hallgren, Emma; Van Ombergen, Angelique; Van de Heyning, Paul H; Wuyts, Floris L

    2015-08-01

    Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS.

  14. The influence of scopolamine on motor control and attentional processes

    PubMed Central

    Bestaven, Emma; Kambrun, Charline; Guehl, Dominique; Cazalets, Jean-René

    2016-01-01

    Background: Motion sickness may be caused by a sensory conflict between the visual and the vestibular systems. Scopolamine, known to be the most effective therapy to control the vegetative symptoms of motion sickness, acts on the vestibular nucleus and potentially the vestibulospinal pathway, which may affect balance and motor tasks requiring both attentional process and motor balance. The aim of this study was to explore the effect of scopolamine on motor control and attentional processes. Methods: Seven subjects were evaluated on four different tasks before and after a subcutaneous injection of scopolamine (0.2 mg): a one-minute balance test, a subjective visual vertical test, a pointing task and a galvanic vestibular stimulation with EMG recordings. Results: The results showed that the reaction time and the movement duration were not modified after the injection of scopolamine. However, there was an increase in the center of pressure displacement during the balance test, a decrease in EMG muscle response after galvanic vestibular stimulation and an alteration in the perception of verticality. Discussion: These results confirm that low doses of scopolamine such as those prescribed to avoid motion sickness have no effect on attentional processes, but that it is essential to consider the responsiveness of each subject. However, scopolamine did affect postural control and the perception of verticality. In conclusion, the use of scopolamine to prevent motion sickness must be considered carefully because it could increase imbalances in situations when individuals are already at risk of falling (e.g., sailing, parabolic flight). PMID:27169000

  15. [Are there cardiovascular adverse effects of inhaled anticholinergics?].

    PubMed

    Nagy, László Béla

    2015-08-02

    The purpose of this review is to discuss the cardiovascular risk associated with inhaled anticholinergics in chronic obstructive pulmonary disease. Several meta-analyses of data for tiotropium raised the possibility of an increased risk for arrhythmia, angina, myocardial infarction, etc. This review includes the data of retrospective studies of databases using databases, randomized controlled trials, and meta-analyses of clinical trials. The conclusions of studies were inconsistent. In most clinical trials the incidence of cardiovascular adverse events was similar in active treatment and placebo groups, especially in patients with previous cardiovascular diseases. Considering meta-analyses, there is little, if any, evidence for the association between anticholinergics and the development of cardiovascular symptoms. The author discusses the presence and function of cholinergic receptor subtypes in human heart, and cardiac functions controlled by the autonomic nervous system via these receptors, their possible role, and pharmacokinetic properties of inhaled anticholinergics. The author concludes that it is not possible to find evidence of increased cardiovascular harm of inhaled anticholinergics.

  16. Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo

    PubMed Central

    Kopera, H.

    1978-01-01

    1 Eighteen healthy male volunteers were treated at random in double-blind conditions with mianserin, amitriptyline, or placebo for 8 days. Measurements were made of various parameters indicative of anticholinergic and blood pressure effects. 2 Mianserin showed no significant anticholinergic effects on any of the measures used. Compared with placebo, mianserin significantly reduced pupil diameter and tended to increase salivary production and increase the distance of the near point. 3 Amitriptyline showed evidence of anticholinergic effects in that salivary production fell to a level significantly lower than that of the mianserin- or placebo-treated subjects. The distance of the near point tended to increase during amitriptyline treatment. Compared with placebo, amitriptyline also significantly reduced pupil diameter on some occasions. 4 Amitriptyline produced postural hypotension to a statistically significant degree, whereas this effect was not observed during mianserin treatment. 5 In conclusion, mianserin in doses of up to 60 mg daily given to healthy males seemed to lack the anticholinergic effects and postural hypotension associated with amitriptyline treatment. PMID:341941

  17. Antiamnesic activity of Syzygium cumini against scopolamine induced spatial memory impairments in rats.

    PubMed

    Alikatte, Kanaka Latha; Akondi, Butchi Raju; Yerragunta, Venu Gopal; Veerareddy, Prabhakar Reddy; Palle, Suresh

    2012-11-01

    We evaluated the Antiamnesic effects of methanolic extract of Syzygium cumini (MESC) on spatial memory impairments induced by scopolamine (1 mg/kg, i.p.), a muscarinic antagonist, using the Radial arm maze, Morris water maze, learned helpless ness tests. Effect of MESC was evaluated and compared to standard drug, piracetam (200 mg/kg, i.p.). The MESC significantly (p<0.05) improved the impairment of short term or working memory induced by scopolamine in the Radial arm maze test, and significantly (p<0.05) reversed cognitive impairments in rats as measured by the learned helplessness test. In addition, MESC decreased escape latencies in the Morris water maze test. The activity of acetylcholinesterase in the brain was inhibited significantly (p<0.05) by treatment with MESC to a level similar to that observed in rats treated with piracetam. Moreover treatment with MESC (200 and 400 mg/kg, p.o.) to scopolamine induced rats significantly (p<0.05) decreased TBARS levels which was accompanied by an increase in the activities of SOD and Catalase. MESC has dose dependent effect and 400 mg/kg dose shown more prominent results when compared to 200 mg/kg dose of MESC. These results indicate that MESC may exert anti-amnesic activity via inhibition of acetylcholinesterase and antioxidant mechanisms in the brain. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

    PubMed

    Hegedűs, Nikolett; Laszy, Judit; Gyertyán, István; Kocsis, Pál; Gajári, Dávid; Dávid, Szabolcs; Deli, Levente; Pozsgay, Zsófia; Tihanyi, Károly

    2015-04-01

    There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials.

  19. The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD.

    PubMed

    Saberi, Farzad; O'Donnell, Denis E

    2005-01-01

    Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a new long-acting inhaled anticholinergic agent with superior pharmacodynamic properties compared with the short-acting anticholinergic, ipratropium bromide. Tiotropium bromide has been consistently shown to have a greater impact than ipratropium bromide on clinically important outcome measures such as health status. The mechanisms of clinical benefit with tiotropium bromide are multifactorial, but improved airway function, which enhances lung emptying and allows sustained deflation of over-inflated lungs, appears to explain improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium bromide therapy has also been associated with reduction in acute exacerbations of COPD as well as reduced hospitalizations. The safety profile of tiotropium bromide is impressive: dry mouth is the most common adverse event and rarely necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has been demonstrated in clinical trials lasting up to 1 year. There is preliminary information that the combination of long-acting anticholinergics and long-acting beta2-adrenoceptor agonists provides additive physiological and clinical benefits. According to recent international guidelines, long-acting bronchodilators should be considered early in the management of symptomatic patients with COPD in order to achieve effective symptom alleviation and reduction in activity limitation. Tiotropium bromide, because of its once-daily administration and its established efficacy and tolerability profile, has emerged as an attractive therapeutic option for this condition.

  20. Hebb-Williams performance and scopolamine challenge in rats with partial immunotoxic hippocampal cholinergic deafferentation.

    PubMed

    Marques Pereira, Patricia; Cosquer, Brigitte; Schimchowitsch, Sarah; Cassel, Jean-Christophe

    2005-01-15

    Recent studies suggested that the cholinergic innervation of the hippocampus is not crucial for spatial learning, but it might be important for other forms of learning. This study assessed the effects of partial immunotoxic cholinergic lesions in the medial septum and concurrent scopolamine challenge in a complex learning task, the Hebb-Williams maze. Long-Evans rats were given intraseptal injections of 192 IgG-saporin (SAPO). Rats injected with phosphate-buffered saline (PBS) served as controls. Starting 25 days after surgery, behavioural performance was assessed in the Hebb-Williams maze test without prior or after injection of scopolamine (0.17 or 0.5 mg/kg, i.p.). In SAPO rats, histochemical analysis showed a 40-45% decrease in the density of hippocampal AChE staining. The number of ChAT-positive cell bodies in the medial septum was also significantly decreased (-56%) and there was a non-significant reduction of the number of parvalbumine-positive neurons. The behavioural results demonstrated that the lesions induced small but significant learning deficits. At 0.17 mg/kg, scopolamine produced more impairments in SAPO rats than in PBS-injected rats, suggesting an additive effect between the partial lesion and the drug. These observations indicate that the Hebb-Williams test may be more sensitive to alterations of septohippocampal cholinergic function, than radial- or water-maze tasks. They also show that subtle learning deficits can be detected after partial lesions of the cholinergic septohippocampal pathways. Finally, the data from the scopolamine challenge are in keeping with clinical results showing higher sensitivity to muscarinic blockade in aged subjects in whom weaker cholinergic functions can be presumed.

  1. Differential effects of MDMA and scopolamine on working versus reference memory in the radial arm maze task.

    PubMed

    Kay, C; Harper, D N; Hunt, M

    2010-02-01

    Previous research has suggested that the disruption to memory-task performance seen following acute exposure to 3,4-methylenedioxymethaphemtamine (MDMA) with rats might best be characterized as reference memory impairment rather than a working memory impairment. The current study specifically compared the effects of MDMA and scopolamine on measures of working versus reference memory in an eight-arm radial maze task. It was predicted that scopolamine would produce a greater impairment with respect to the working memory component of the task, whereas MDMA would produce a greater impairment to reference memory. On each trial rats were allowed to make a total of four arm visits in order to collect the reinforcers located at the end of different arms in the maze. Working memory errors were indicated by re-visiting an already visited arm during a trial, whereas visiting an arm that was never baited on any trial indicated a reference memory error. Using a within subjects design, rats were exposed to a range of doses of scopolamine and MDMA administered acutely. An interaction between drug type and memory error type was found. Specifically, scopolamine produced more working memory errors than reference memory errors, while MDMA produced the opposite pattern of significantly more reference memory errors compared to working memory error. This finding supported the hypothesis that MDMA disrupts reference memory processes in terms of an impairment in the strategies or rules used for solving memory tasks. Copyright 2009 Elsevier Inc. All rights reserved.

  2. Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice.

    PubMed

    Jeong, Eun Ju; Lee, Ki Yong; Kim, Seung Hyun; Sung, Sang Hyun; Kim, Young Choong

    2008-06-24

    The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.

  3. Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain.

    PubMed

    Ahmad, Aliya; Ramasamy, Kalavathy; Jaafar, Siti Murnirah; Majeed, Abu Bakar Abdul; Mani, Vasudevan

    2014-03-01

    The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1β and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

    PubMed

    Kim, Hyun-Bum; Lee, Seok; Hwang, Eun-Sang; Maeng, Sungho; Park, Ji-Ho

    2017-10-21

    Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The role of nicotinic receptors in the amelioration of cholinesterase inhibitors in scopolamine-induced memory deficits.

    PubMed

    Masuoka, Takayoshi; Kamei, Chiaki

    2009-10-01

    Nicotine receptors in the brain are closely related with memory amelioration induced by cholinesterase inhibitors. The present study was undertaken to clarify the role of nicotinic receptors in the ameliorative effects of cholinesterase inhibitors on scopolamine-induced memory deficit. Drug effects were measured using an eight-arm radial maze with four arms baited. Hippocampal theta rhythm during the radial maze task was also recorded with a polygraph system using a telemetric technique. Scopolamine (0.5 mg/kg, i.p.) caused a spatial memory deficit as well as an increase in hippocampal theta power during radial maze performance. Pilocarpine, nicotine, physostigmine, and donepezil antagonized the effects of scopolamine. The ameliorative effects of nicotine, physostigmine, and donepezil but not piocarpine on memory performance and hippocampal theta activity were reversed by mecamylamine. These results indicate that nicotinic receptors have an essential role in the ameliorative effects of cholinesterase inhibitors in both scopolamine-induced memory deficit and the increase in hippocampal theta activity.

  6. Transdermal scopolamine for prevention of motion sickness : clinical pharmacokinetics and therapeutic applications.

    PubMed

    Nachum, Zohar; Shupak, Avi; Gordon, Carlos R

    2006-01-01

    -term use of the drug. The adverse effects produced by TTS-S, although less frequent, are qualitatively typical of those reported for the oral and parenteral formulations of this agent. Dry mouth occurs in about 50-60% of subjects, drowsiness in up to 20%, and allergic contact dermatitis in 10%. Transient impairment of ocular accommodation has also been observed, in some cases possibly the result of finger-to-eye contamination. Low-dose pyridostigmine was found effective in preventing cycloplegia but not mydriasis. Adverse CNS effects, including toxic psychosis (mainly in elderly and paediatric patients), have been reported only occasionally, as have difficulty in urinating, headache, rashes and erythema. Adverse effects were not correlated with plasma scopolamine concentrations. TTS-S produced only about half the incidence of drowsiness caused by oral dimenhydrinate or cinnarizine, and a level of adverse effects similar to that found with oral meclizine. Performance is not affected by short-term use. Prolonged or repeated application may cause some impairment of memory storage for new information. However, sea studies revealed significantly less reports of a decrement in performance or drowsiness due to prevention of sea sickness. The recommended dosage is a single TTS-S patch applied to the postauricular area at least 6-8 hours before the anti-motion sickness effect is required. For faster protection, the patch may be applied 1 hour before the journey in combination with oral scopolamine (0.3 or 0.6 mg). After 72 hours, the patch should be removed and a new one applied behind the opposite ear. Its place in therapy is mainly on long journeys (6-12 hours or longer), to avoid repeated oral doses, or when oral therapy is ineffective or intolerable.

  7. Anticholinergic Versus Botulinum Toxin A Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC Trial

    PubMed Central

    Visco, Anthony G.; Brubaker, Linda; Richter, Holly E.; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A.; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

    2011-01-01

    This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 unit of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC Trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost-effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intradetrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intradetrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intradetrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. PMID:22008247

  8. Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.

    PubMed

    Konar, Arpita; Shah, Navjot; Singh, Rumani; Saxena, Nishant; Kaul, Sunil C; Wadhwa, Renu; Thakur, Mahendra K

    2011-01-01

    Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive. In the present study, we have investigated (i) the effects of scopolamine on the molecules involved in neuronal and glial plasticity both in vivo and in vitro and (ii) their recovery by alcoholic extract of Ashwagandha leaves (i-Extract). As a drug model, scopolamine hydrobromide was administered intraperitoneally to mice and its effect on the brain function was determined by molecular analyses. The results showed that the scopolamine caused downregulation of the expression of BDNF and GFAP in dose and time dependent manner, and these effects were markedly attenuated in response to i-Extract treatment. Similar to our observations in animal model system, we found that the scopolamine induced cytotoxicity in IMR32 neuronal and C6 glioma cells. It was associated with downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP-43 and glial cell marker GFAP and with upregulation of DNA damage--γH2AX and oxidative stress--ROS markers. Furthermore, these molecules showed recovery when cells were treated with i-Extract or its purified component, withanone. Our study suggested that besides cholinergic blockade, scopolamine-induced memory loss may be associated with oxidative stress and Ashwagandha i-Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses.

  9. Protective Role of Ashwagandha Leaf Extract and Its Component Withanone on Scopolamine-Induced Changes in the Brain and Brain-Derived Cells

    PubMed Central

    Singh, Rumani; Saxena, Nishant; Kaul, Sunil C.; Wadhwa, Renu; Thakur, Mahendra K.

    2011-01-01

    Background Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive. In the present study, we have investigated (i) the effects of scopolamine on the molecules involved in neuronal and glial plasticity both in vivo and in vitro and (ii) their recovery by alcoholic extract of Ashwagandha leaves (i-Extract). Methodology/Principal Findings As a drug model, scopolamine hydrobromide was administered intraperitoneally to mice and its effect on the brain function was determined by molecular analyses. The results showed that the scopolamine caused downregulation of the expression of BDNF and GFAP in dose and time dependent manner, and these effects were markedly attenuated in response to i-Extract treatment. Similar to our observations in animal model system, we found that the scopolamine induced cytotoxicity in IMR32 neuronal and C6 glioma cells. It was associated with downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP-43 and glial cell marker GFAP and with upregulation of DNA damage- γH2AX and oxidative stress- ROS markers. Furthermore, these molecules showed recovery when cells were treated with i-Extract or its purified component, withanone. Conclusion Our study suggested that besides cholinergic blockade, scopolamine-induced memory loss may be associated with oxidative stress and Ashwagandha i-Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses. PMID:22096544

  10. Scopolamine-induced deficits in social memory in mice: reversal by donepezil.

    PubMed

    Riedel, G; Kang, S H; Choi, D Y; Platt, B

    2009-12-01

    Deficits in social behaviour is a characteristic of numerous mental disorders including autism, schizophrenia, depression and Alzheimer's disease. For the assessment of pharmacological and genetic experimental disease models, conventional social interaction tasks bear the uncertainty that any drug-induced abnormality of the investigator may feed back to the drug-free companion modifying its reactions. A considerable technical improvement was recently reported by Moy et al. [Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson T, et al. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behaviours in mice. Genes Brain Behav 2004;3:287-302] in which the drug free partner is confined to a small cage and social contacts of the investigator are recorded uncontaminated of any social reactions of the stranger. Using this novel behavioural paradigm, we here show in C57Bl/6 female mice that sociability (social interaction with a stranger mouse) is not impaired after administration of the anxiolytic diazepam (0.1-1 mg/kg) or the muscarinic antagonist scopolamine hydrobromide (0.1-1 mg/kg). However, social memory tested after a short time interval was impaired by both drugs in a dose-dependent manner (diazepam: > or = 0.5mg/kg; scopolamine: > or = 0.3mg/kg). The scopolamine-induced short-term memory deficit was reversed to normal by the choline esterase inhibitor donepezil (1 mg/kg). Given this dependence of social recognition on the cholinergic system, combined with the clinical observation of reduced social contacts in dementia patients, sociability may offer a novel endpoint biomarker with translational value in experimental models of cognitive dysfunction.

  11. CDP-choline attenuates scopolamine induced disruption of prepulse inhibition in rats: involvement of central nicotinic mechanism.

    PubMed

    Uslu, Gulsah; Savci, Vahide; Buyukuysal, Levent R; Goktalay, Gokhan

    2014-05-21

    It has been shown that cholinergic system plays an important role in schizophrenia-associated cognitive deficits, therefore cholinergic drugs are novel targets for the treatment of cognitive deficits seen in schizophrenia. We aimed to test the effects of CDP-choline on sensorimotor gating functioning, which is an important function for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. In this study, prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning, and the effects of CDP-choline on scopolamine induced PPI disruption were evaluated in rats. Furthermore, the contribution of the cholinergic mechanism in these effects was determined. CDP-choline (75, 250, 500mg/kg) by itself had no effect on the PPI in naïve animals. Scopolamine (0.4mg/kg; s.c.) significantly decreased the PPI levels and intraperitoneal administration of CDP-choline (250mg/kg) attenuated the effects of scopolamine. A non-specific nicotinic receptor antagonist, mecamylamine and an alpha 7 nicotinic receptor (α7-nAChR) antagonist, methyllycaconitine were used to investigate the mechanism underlying the effects of CDP-choline. Mecamylamine (3mg/kg; s.c.), and methyllycaconitine (10μg; i.c.v.) completely blocked the reversal effects of CDP-choline on scopolamine induced disruption of PPI. These results demonstrate that exogenous administration of CDP-choline attenuates scopolamine induced PPI disruption and show that the activation of central α7-nAChR may play a critical role in this effect.

  12. Procognitive effect of AC-3933 in aged mice, and synergistic effect of combination with donepezil in scopolamine-treated mice.

    PubMed

    Hashimoto, Takashi; Hatayama, Yuki; Nakamichi, Keiko; Yoshida, Naoyuki

    2014-12-15

    We have previously reported that AC-3933, a newly developed benzodiazepine receptor partial inverse agonist, facilitates acetylcholine release in the hippocampus and ameliorates scopolamine-induced memory deficits in rats. To further confirm the procognitive effect of AC-3933, we assessed in this study the beneficial effects of this compound in aged mice using the Y-maze and object recognition tests. In addition, we investigated the synergistic effect of AC-3933 and donepezil, a cholinesterase inhibitor, on scopolamine-induced memory impairment in mice. In aged mice, oral administration of AC-3933 at doses of 0.05-0.1 mg/kg and 0.05 mg/kg significantly improved spatial working memory and episodic memory, respectively. In scopolamine-treated mice, both AC-3933 and donepezil significantly ameliorated memory deficits in the Y-maze test at doses of 0.3-3 mg/kg and 10-15 mg/kg, respectively. The beneficial effect of AC-3933, but not that of donepezil, on scopolamine-induced memory impairment was antagonized by flumazenil, a benzodiazepine receptor antagonist, indicating that the procognitive action of AC-3933 arises via a mechanism different from that of donepezil. Co-administration of donepezil at the suboptimal dose of 3 mg/kg with AC-3933 at doses of 0.1-1 mg/kg significantly ameliorated scopolamine-induced memory impairment, suggesting that AC-3933 potentiates the effect of donepezil on memory impairment induced by cholinergic hypofunction. These findings indicate that AC-3933 not only has good potential as a cognitive enhancer by itself, but also is useful as a concomitant drug for the treatment of Alzheimer׳s disease.

  13. Anticholinergic toxicity from nightshade berry poisoning responsive to physostigmine.

    PubMed

    Ceha, L J; Presperin, C; Young, E; Allswede, M; Erickson, T

    1997-01-01

    The woody nightshade, Solanum dulcamara, belongs to the genus Solanum and its primary toxin is solanine. We report a large nightshade ingestion in a 4-yr-old girl who presented to the emergency department in acute anticholinergic crisis. The child was given 0.2 mg of intravenous physostigmine (0.02 mg/kg). Within 50 min, the patient received two additional equal doses with complete resolution of symptoms. After 36 h of observation, the child was discharged. Our patient presented with symptoms more suggestive of the deadly nightshade species, Atropa belladonna, which is native to Europe; however, a detailed laboratory analysis of the suspect berries revealed no atropine or hyoscyamine. Analysis did reveal sterols consistent with solanine. This is a unique case presentation of woody nightshade, S. dulcamara, poisoning presenting with anticholinergic crisis and responding to physostigmine.

  14. Anticholinergic syndrome and supraventricular tachycardia caused by lavender tea toxicity.

    PubMed

    Acikalin, Ayca; Gulen, Muge; Kara, Banu; Icme, Ferhat; Cagliyan, Caglar Emre; Satar, Salim

    2012-01-01

    Lavender plants have been used for their cosmetic and biologic benefits for many centries. Extracts from Lavandula plants have been found to cause antimuscarinic effects by blocking sodium and calcium ion channels in in vitro and in vivo studies. We present a case of poisoning by ingestion of tea made from Lavender stoechas ( grass). The patient was admitted to our emergency department with supraventricular tachycardia due to anticholinergic syndrome triggered by drinking lavender tea. On electrocardiography, a narrow QRS complex tachycardia was evident. After carotid sinus massage, the patient immediately returned to sinus rhythm. There are no reported data about the toxicity of Lavender stoechas plants with respect to supraventricular tachycardia, anticholinergic syndrome or sympathetic nerve activity.

  15. [Anticholinergic syndrome after intoxication by lupine seeds (Tourmos)].

    PubMed

    Awada, Adnan; Atallah, David; Zoghbi, Antoine

    2011-01-01

    Yellow lupine seeds (Tourmos) are frequently used as snack in Lebanon but their potential toxicity is extremely rare (five published cases) and often undiagnosed. Two patients presented with anticholinergic syndrome (mydriasis, mouth dryness, palpitations, general malaise) after ingestion of 200-500 g of bitter lupine seeds (not soaked enough in water). No other cause of intoxication was found, and symptoms disappeared spontaneously in 24-36h. Yellow lupine seeds need a long preparation (boiling then soaking with several changes of water) to debitter before consumption. The spontaneous bitter taste is mainly due to the presence of a toxic substance with anticholinergic properties, lupanine. An insufficient preparation or a preference for bitter lupin can result in intoxication.

  16. Effects of rivastigmine and memantine alone and in combination on learning and memory in rats with scopolamine-induced amnesia

    PubMed Central

    Yanev, Peter Georgiev; Dimitrova, Darinka Slavcheva

    2015-01-01

    Background Cholinesterase inhibitors and glutamate blockers are commonly used for the treatment of cognitive impairment in Alzheimer’s disease. The aim was to evaluate the effects of rivastigmine and memantine alone or in combination in rats with scopolamine-impaired memory. Method 5 groups of rats were used: control, scopolamine (model), model with rivastigmine, model with memantine, and model with both drugs. Active avoidance test was performed and the number of conditioned responses, unconditioned responses and intertrial crossing were recorded. Passive avoidance tests step-through with criteria latency of reaction 180 s in the light chamber and step-down with criteria latency of reaction 60 s on the platform were done. Results Control rats learned the task and kept it on memory tests. Scopolamine treated rats failed to perform it. The rivastigmine, memantine and its combination groups showed increased CRs during learning and memory retention tests. In both passive avoidance tests an increased latency of reaction was observed in the drug treated groups. Conclusion The combination of both drugs rivastigmine and memantine is more effective than the use of the single drug in cognitive impaired rats. Cholinesterase inhibitors and NMDA blockers may be combined in the treatment of different kind of dementias.

  17. Scopolamine and MK801-induced working memory deficits in rats are not reversed by CBD-rich cannabis extracts.

    PubMed

    Fadda, Paola; Robinson, Lianne; Fratta, Walter; Pertwee, Roger G; Riedel, Gernot

    2006-04-03

    Smoking marijuana causes working and short-term memory deficits, an effect that is mediated by cannabinoid receptor (CB1) activation in the brain. While this may be due to the main psychoactive constituent Delta9-tetrahydrocannabinol (Delta9-THC), plant extracts also contain other cannabinoid and terpenoid compounds with unknown properties. Towards this end, we have recently shown that high concentrations of plant extracts rich in cannabidiol (CBD) can reverse working memory deficits induced by Delta9-THC which is a remaining contaminant of this extract [Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential effects of THC- and CBD-rich cannabis-extracts on working memory in rats. Neuropahrmacology 2004;47:1170-9]. Since this effect was dose-dependent and indicative of memory enhancing qualities of the CBD-rich extract, this prompted a wider investigation into the effects of CBD on other forms of amnesia in order to determine the mechanism of action and to reveal its potency against anticholinergic and antiglutamatergic agents. We employed a spatial delayed matching to position task in the open-field water maze. Both scopolamine (0.2 mg/kg i.p.) and dizocilpine (MK801: 0.1mg/kg i.p.) impaired working memory at delays of 30 s and 4 h. Two doses of CBD-rich extracts (5 and 10 mg/kg), which did not affect working memory when given alone, were unable to reverse these deficits when co-administered with scopolamine or MK801. These data suggest that reversal of working memory deficits by CBD-rich extracts are specific to the cannabinoid system and do not compensate for acutely induced cholinergic or glutamatergic receptor hypoactivity.

  18. Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

    PubMed Central

    Izquierdo, José Luis; Paredero, José Manuel; Piedra, Raul

    2016-01-01

    Introduction The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence. Methods We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014. Results During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014. Conclusion The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. PMID:26929614

  19. Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence

    PubMed Central

    Visco, Anthony G.; Brubaker, Linda; Richter, Holly E.; Nygaard, Ingrid; Paraiso, Marie Fidela R.; Menefee, Shawn A.; Schaffer, Joseph; Lowder, Jerry; Khandwala, Salil; Sirls, Larry; Spino, Cathie; Nolen, Tracy L.; Wallace, Dennis; Meikle, Susan F.

    2012-01-01

    BACKGROUND Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed. METHODS We performed a double-blind, double-placebo–controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events. RESULTS Of 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P = 0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P = 0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P = 0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P = 0.01) and urinary tract infections (13% vs. 33%, P<0.001). CONCLUSIONS Oral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of

  20. An Animal Model of Drug-Induced Thermoregulatory and Endurance Decrements

    DTIC Science & Technology

    1992-01-01

    suppression. Anticholinesterase drugs are used clinically for treatment of myasthenia gravis, Alzheimer’s disease , anticholinergic syndrome, and as a pretreatment against potential organophosphorus exposure.

  1. Multi-development-HPTLC method for quantitation of hyoscyamine, scopolamine and their biosynthetic precursors in selected solanaceae plants grown in natural conditions and as in vitro cultures.

    PubMed

    Jaremicz, Zbigniew; Luczkiewicz, Maria; Kisiel, Mariusz; Zárate, Rafael; El Jaber-Vazdekis, Nabil; Migas, Piotr

    2014-01-01

    Hyoscyamine and scopolamine, anti-cholinergic agents widely used in medicine, are typically obtained from plants grown under natural conditions. Since field cultivation entails certain difficulties (changeable weather, pests, etc.), attempts have been made to develop a plant in vitro culture system as an alternative source for the production of these compounds. During experiments to locate the limiting steps in the biotechnological procedure, it is important to monitor not only the levels of the final products but also the changes in the concentration of their precursors. To develop a HPTLC method for the separation and quantitation of the main tropane alkaloids hyoscyamine and scopolamine, their respective direct precursors littorine and anisodamine, and cuscohygrine, a product of a parallel biosynthetic pathway that shares a common precursor (N-methyl-∆(1) -pyrrolium cation) with tropane alkaloids. Using alkaloid extracts from Atropa baetica hairy roots, different TLC chromatographic systems and developing procedures were investigated. Full separation of all compounds was obtained on HPTLC Si60 F254 plates preconditioned with mobile phase vapours (chloroform:methanol:acetone:25% ammonia ratios of 75:15:10:1.8, v/v/v/v). The chromatograms were developed twice (at distances of 4.0 and 3.0 cm) in a Camag twin trough chamber and visualised with Dragendorff's reagent. Densitometric detection (λ = 190 and 520 nm) was used for quantitative analyses of the different plant samples. This method can be recommended for quantitation of hyoscyamine, scopolamine, anisodamine, littorine and cuscohygrine in different plant material (field grown vs. in vitro cultures). Copyright © 2013 John Wiley & Sons, Ltd.

  2. Intra- and inter-laboratory validation of a dipstick immunoassay for the detection of tropane alkaloids hyoscyamine and scopolamine in animal feed.

    PubMed

    Mulder, Patrick P J; von Holst, Christoph; Nivarlet, Noan; van Egmond, Hans P

    2014-01-01

    Tropane alkaloids (TAs) are toxic secondary metabolites produced by plants of, inter alia, the genera Datura (thorn apple) and Atropa (deadly nightshade). The most relevant TAs are (-)-L-hyoscyamine and (-)-L-scopolamine, which act as antagonists of acetylcholine muscarinic receptors and can induce a variety of distinct toxic syndromes in mammals (anti-cholinergic poisoning). The European Union has regulated the presence of seeds of Datura sp. in animal feeds, specifying that the content should not exceed 1000 mg kg(-1) (Directive 2002/32/EC). For materials that have not been ground, visual screening methods are often used to comply with these regulations, but these cannot be used for ground materials and compound feeds. Immunological assays, preferably in dipstick format, can be a simple and cost-effective approach to monitor feedstuffs in an HACCP setting in control laboratories. So far no reports have been published on immunoassays that are capable of detecting both hyoscyamine and scopolamine with equal sensitivity and that can be used, preferably in dipstick format, for application as a fast screening tool in feed analysis. This study presents the results obtained for the in-house and inter-laboratory validation of a dipstick immunoassay for the detection of hyoscyamine and scopolamine in animal feed. The target level was set at 800 µg kg(-1) for the sum of both alkaloids. By using a representative set of compound feeds during validation and a robust study design, a reliable impression of the relevant characteristics of the assay could be obtained. The dipstick test displayed similar sensitivity towards the two alkaloids and it could be concluded that the test has a very low probability of producing a false-positive result at blank level or a false-negative result at target level. The assay can be used for monitoring of TAs in feedstuffs, but has also potential as a quick screening tool in food- or feed-related poisonings.

  3. Attenuation of scopolamine-induced cognitive dysfunction by obovatol.

    PubMed

    Choi, Dong-Young; Lee, Young-Jung; Lee, Sun Young; Lee, Yoot Mo; Lee, Hyun Hee; Choi, Im Seop; Oh, Ki-Wan; Han, Sang Bae; Nam, Sang-Yoon; Hong, Jin Tae

    2012-07-01

    Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly people. The disease is pathologically characterized by extracellular deposition of beta-amyloid peptide (Aβ), cholinergic neurodegeneration and elevation of acetylcholine esterase (AChE) activity in the affected regions. In this study, we investigated the effects of obovatol on memory dysfunction, which was caused by scopolamine. Obovatol (0.2, 0.5 and 1 mg/kg for 7 day) attenuated scopolamine (1 mg/kg, i.p.)-induced amnesia in a dose-dependent manner, as revealed by the Morris water maze test and step-through passive avoidance test. Mechanism studies exhibited that obovatol dose-dependently alleviated scopolamine-induced increase in Aβ generation and β-secretase activity in the cortex and hippocampus. Obovatol also attenuated scopolamine-induced rise in AChE activity in the cortex and hippocampus. Obovatol might rescue scopolamine-mediated impaired learning and memory function by attenuating Aβ accumulation and stabilizing cholinergic neurotransmission, which suggests that the natural compound could be a useful agent for the prevention of the development or progression of AD neurodegeneration.

  4. Sulforaphane alleviates scopolamine-induced memory impairment in mice.

    PubMed

    Lee, Siyoung; Kim, Jisung; Seo, Sang Gwon; Choi, Bo-Ryoung; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

    2014-07-01

    Sulforaphane, an organosulfur compound present in cruciferous vegetables, has been shown to exert neuroprotective effects in experimental in vitro and in vivo models of neurodegeneration. To determine whether sulforaphane can preserve cognitive function, we examined its effects on scopolamine-induced memory impairment in mice using the Morris water maze test. Sulforaphane (10 or 50mg/kg) was administered to C57BL/6 mice by oral gavage for 14 days (days 1-14), and memory impairment was induced by intraperitoneal injection of scopolamine (1mg/kg) for 7 days (days 8-14). Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity in the hippocampus and frontal cortex, as indicated by a decreased acetylcholine (ACh) level and an increased acetylcholinesterase (AChE) activity. Sulforaphane significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex. These effects of sulforaphane on cholinergic system reactivity were confirmed in vitro. Sulforaphane (10 or 20μM) increased the ACh level, decreased the AChE activity, and increased ChAT expression in scopolamine-treated primary cortical neurons. These observations suggest that sulforaphane might exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment. Copyright © 2014. Published by Elsevier Ltd.

  5. Antiamnesic effect of stevioside in scopolamine-treated rats.

    PubMed

    Sharma, Deepika; Puri, Munish; Tiwary, Ashok K; Singh, Nirmal; Jaggi, Amteshwar Singh

    2010-06-01

    The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) in animals. Morris water maze (MWM) test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE) activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Pretreatment of stevioside (250 mg/kg dose orally) significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions.

  6. Antiamnesic effect of stevioside in scopolamine-treated rats

    PubMed Central

    Sharma, Deepika; Puri, Munish; Tiwary, Ashok K.; Singh, Nirmal; Jaggi, Amteshwar Singh

    2010-01-01

    The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) in animals. Morris water maze (MWM) test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE) activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Pretreatment of stevioside (250 mg/kg dose orally) significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions. PMID:20871768

  7. Mechanisms of antimotion sickness drugs

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Wood, M. J.; Manno, B. R.; Redetzki, H. M.

    1987-01-01

    Eight subjects, male and female, were rotated using the step method to progressively increase the speed of rotation (+2 rpm) after every 40 head movements to a maximum of 35 rpm. The end point for motion sickness was the Graybiel Malaise III total of symptoms short of frank nausea. The drug treatments were placebo, scopolamine 0.6 mg and 1 mg, scopolamine 0.6 mg/d-amphetamine 10 mg, scopolamine 1 mg/d-amphetamine 10 mg, and amphetamine 10 mg. Scopolamine increased tolerated head movements over placebo level by + 81; scopolamine 1 mg + 183; d-amphetamine by + 118; scopolamine 0.6/d-amphetamine by + 165; and scopolamine 1 mg/d-amphetamine 10 mg by + 201. The drugs effective in preventing motion sickness are considered to be divided into those with central acetylcholine blocking activity and those which enhance norepinephrine activity. A combination of both of these actions produces the most effective antimotion sickness medications. It is concluded that the balance between the acetylcholine and norepinephrine activity in the CNS appears to be responsible for motion sickness.

  8. Mechanisms of antimotion sickness drugs

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Wood, M. J.; Manno, B. R.; Redetzki, H. M.

    1987-01-01

    Eight subjects, male and female, were rotated using the step method to progressively increase the speed of rotation (+2 rpm) after every 40 head movements to a maximum of 35 rpm. The end point for motion sickness was the Graybiel Malaise III total of symptoms short of frank nausea. The drug treatments were placebo, scopolamine 0.6 mg and 1 mg, scopolamine 0.6 mg/d-amphetamine 10 mg, scopolamine 1 mg/d-amphetamine 10 mg, and amphetamine 10 mg. Scopolamine increased tolerated head movements over placebo level by + 81; scopolamine 1 mg + 183; d-amphetamine by + 118; scopolamine 0.6/d-amphetamine by + 165; and scopolamine 1 mg/d-amphetamine 10 mg by + 201. The drugs effective in preventing motion sickness are considered to be divided into those with central acetylcholine blocking activity and those which enhance norepinephrine activity. A combination of both of these actions produces the most effective antimotion sickness medications. It is concluded that the balance between the acetylcholine and norepinephrine activity in the CNS appears to be responsible for motion sickness.

  9. Effect of Anticholinergic Use for the Treatment of Overactive Bladder on Cognitive Function in Post-Menopausal Women

    PubMed Central

    Geller, Elizabeth J.; Crane, Andrea K.; Wells, Ellen C.; Robinson, Barbara L.; Jannelli, Mary L.; Khandelwal, Christine M.; Connolly, AnnaMarie; Parnell, Brent A.; Matthews, Catherine A.; Dumond, Julie B.; Busby-Whitehead, Jan

    2013-01-01

    Background Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs including cognitive changes. Objective To investigate the effect of an anticholinergic medication on cognitive function in postmenopausal women being treated for OAB. Study Design Prospective cohort study conducted from January to December 2010, with 12-week follow-up after medication initiation. Setting Urogynecology clinic at one academic medical center. Patients Women age 55 or older seeking treatment for OAB and opting for anticholinergic therapy were recruited. Intervention Baseline cognitive function was assessed via the Hopkins Verbal Learning Test – Revised Form (HVLT-R) (and its 5 subscales), the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality of life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance. Main Outcome Measure Change in HVLT-R score at Week 4 after medication initiation, compared to baseline (pre-medication) score. Results Of 50 women enrolled, 35 completed the assessment. Average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p=0.037), HVLT-R Delayed Recognition subscale (p=0.011) and HVLT-R Recognition Bias subscale (p=0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p=0.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini

  10. LC determination of atropine sulfate and scopolamine hydrobromide in pharmaceuticals.

    PubMed

    Ceyhan, T; Kartal, M; Altun, M L; Tülemis, F; Cevheroglu, S

    2001-06-01

    An accurate, simple, reproducible and sensitive method for the determination of atropine sulfate and scopolamine hydrobromide has been developed and validated. Atropine sulfate and scopolamine hydrobromide were separated using a microBondapack C(18) column by isocratic elution with flow rate 1.0 ml/min. The mobile phase composition was methanol, water, formic acid (165:35:1; v/v/v) and pH adjusted 8.3 with triethylamine. The samples were detected at 230 nm using photo-diode array detector. The linear range of detection for atropine sulfate (I) and scopolamine hydrobromide (II) were between 10.38 and 1038 microg/ml with a limit of quantification (LOQ) of 10.38, 10.00 and 1034 microg/ml with an LOQ of 10.00 microg/ml respectively. The linearity, range, peak purity, selectivity, system performance parameters, precision, accuracy, robustness and ruggedness for (I) and (II) were also shown acceptable values.

  11. Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

    NASA Technical Reports Server (NTRS)

    Tietze, Karen J.

    1990-01-01

    Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

  12. Male overactive bladder: the role of urodynamics and anticholinergics.

    PubMed

    MacDiarmid, Scott; Rogers, Alexandra

    2007-01-01

    Millions of men suffer from overactive bladder and lower urinary tract symptoms. The adverse effects on quality of life and costs associated with the condition have been well described. In men, the pathophysiology of lower urinary tract symptoms may be from a number of causes including bladder outlet obstruction, detrusor overactivity, or both. Increasing data and clinical experience support the efficacy and safety of anticholinergics in men; the rate of urinary retention has been equal to that of placebo in short-term studies. Urodynamics play a vital role in defining the bladder and/or outlet dysfunction and help direct one's therapy.

  13. Neonatal treatment with scopolamine butylbromide prevents metabolic dysfunction in male rats

    PubMed Central

    Malta, Ananda; Souza, Aline Amenencia de; Ribeiro, Tatiane Aparecida; Francisco, Flávio Andrade; Pavanello, Audrei; Prates, Kelly Valério; Tófolo, Laize Peron; Miranda, Rosiane Aparecida; Oliveira, Júlio Cezar de; Martins, Isabela Peixoto; Previate, Carina; Gomes, Rodrigo Mello; Franco, Claudinéia Conationi da Silva; Natali, Maria Raquel Marçal; Palma-Rigo, Kesia; Mathias, Paulo Cezar de Freitas

    2016-01-01

    We tested whether treatment with a cholinergic antagonist could reduce insulin levels in early postnatal life and attenuate metabolic dysfunctions induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SLs, 3 pups/dam) and normal litters (NLs, 9 pups/dam) were used in models of early overfeeding and normal feeding, respectively. During the first 12 days of lactation, animals in the SL and NL groups received scopolamine butylbromide (B), while the controls received saline (S) injections. The drug treatment decreased insulin levels in pups from both groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, vagus nerve activity, fat tissue accretion, insulinemia, leptinemia, body weight gain and food intake. Low glucose and cholinergic insulinotropic effects were observed in pancreatic islets from both groups. Low protein expression was observed for the muscarinic M3 acetylcholine receptor subtype (M3mAChR), although M2mAChR subtype expression was increased in SL-B islets. In addition, beta-cell density was reduced in drug-treated rats. These results indicate that early postnatal scopolamine butylbromide treatment inhibits early overfeeding-induced metabolic dysfunctions in adult rats, which might be caused by insulin decreases during lactation, associated with reduced parasympathetic activity and expression of M3mAChR in pancreatic islets. PMID:27561682

  14. Nootropic activity of Crataeva nurvala Buch-Ham against scopolamine induced cognitive impairment

    PubMed Central

    Bhattacharjee, Atanu; Shashidhara, Shastry Chakrakodi; Saha, Santanu

    2015-01-01

    Loss of cognition is one of the age related mental problems and a characteristic symptom of neurodegenerative disorders like Alzheimer’s. Crataeva nurvala Buch-Ham, a well explored traditional Indian medicinal plant of Westernghats, is routinely used as folkloric medicine to treat various ailments in particular urolithiasis and neurological disorders associated with cognitive dysfunction. The objective of the study was to evaluate the nootropic activity of Crataeva nurvala Buch-Ham stem bark in different learning and memory paradigm viz. Elevated plus maze and Y-maze against scopolamine induced cognitive impairment. Moreover, to elucidate possible mechanism, we studied the influence of Crataeva nurvala ethanolic extract on central cholinergic activity via estimating the whole brain acetyl cholinesterase enzyme. Ethanolic extracts of Crataeva nurvala (100, 200 and 400 mg/kg body weight) were administered to adult Wistar rats for successive seven days and the acquisition, retention and retrieval of spatial recognition memory was determined against scopolamine (1 mg/kg, i.p.) induced amnesia through exteroceptive behavioral models viz. Elevated plus maze and Y-maze models. Further, whole brain acetyl cholinesterase enzyme was estimated through Ellman’s method. Pretreatment with Crataeva nurvala ethanolic extract significantly improved spatial learning and memory against scopolamine induced amnesia. Moreover, Crataeva nurvala extract decreased rat brain acetyl cholinesterase activity in a dose dependent manner and comparable to the standard drug Piracetam. The results indicate that ethanolic extract of Crataeva nurvala might be a useful as nootropic agent to delay the onset and reduce the severity of symptoms associated with dementia and Alzheimer’s disease. The underlying mechanism of action of its nootropic potentiality might be attributed to its anticholinesterase property. PMID:27065767

  15. Activation of dopamine D1 receptors in the medial septum improves scopolamine-induced amnesia in the dorsal hippocampus.

    PubMed

    Zarrindast, Mohammad Reza; Ardjmand, Abolfazl; Ahmadi, Shamseddin; Rezayof, Ameneh

    2012-04-01

    In the present study, we investigated the influence of intra-medial septum (intra-MS) injections of dopamine D1 receptor agents on amnesia induced by intra-CA1 injections of a muscarinic acetylcholine receptor antagonist, scopolamine. This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that in the animals that received post-training intra-MS injections of saline, intra-CA1 administrations of scopolamine (0.75, 1, and 2 μg/rat) decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-MS injections of a dopamine D1 receptor agonist, SKF38393 at doses of 0.1, 0.15, and 0.3 μg/rat had no effect, but at dose of 0.5 μg/rat impaired IA memory consolidation. Interestingly, intra-MS injections of SKF38393 (0.15, 0.3 and 0.5 μg/rat) significantly prevented amnesia induced by intra-CA1 injections of scopolamine (1 μg/rat). Intra-MS injections of a dopamine D1 receptor antagonist, SCH23390 (0.5 and 0.75 μg/rat) by itself impaired IA memory consolidation, and also at dose of 0.75 μg/rat increased amnesia induced by intra-CA1 administrations of an ineffective dose of scopolamine (0.5 μg/rat). Post-training intra-MS injections of ineffective doses of SCH23390 (0.1, 0.3 and 0.5 μg/rat) prevented an effective dose of SKF38393 response to the impaired effect of scopolamine. These results suggest that dopamine D1 receptors in the MS via projection neurons to the hippocampus affect impairment of memory consolidation induced by intra-CA injections of scopolamine.

  16. Nocturnal Elevation of Plasma Melatonin and Urinary 5-Hydroxyindoleacetic Acid in Young Men: Attempts at Modification by Brief Changes in Environmental Lighting and Sleep and by Autonomic Drugs.

    DTIC Science & Technology

    DIURNAL VARIATIONS, *BIOLOGICAL RHYTHMS, *AUTONOMIC AGENTS, HUMANS, BIOCHEMISTRY, LIGHT, METABOLISM, DARKNESS, PHYSIOLOGY, DRUGS, SECRETION, INDOLES, ACETIC ACID , ENDOCRINOLOGY, PINEAL GLAND, ISOPROTERENOL, SCOPOLAMINE.

  17. Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

    2009-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on

  18. Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

    2009-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on

  19. Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment?

    PubMed

    Desmarais, Julie Eve; Beauclair, Linda; Margolese, Howard C

    2012-09-01

    Anticholinergic agents are usually prescribed to prevent or treat antipsychotic-induced extrapyramidal symptoms. Their long-term benefits are questionable and they carry diverse adverse effects, including cognitive impairment and worsening of tardive dyskinesia. This literature review explores the impact of anticholinergic medication discontinuation on movement disorders, cognition and psychopathology in patients receiving antipsychotics. Medline, Embase and PsycInfo were searched from 1950 to July 2011 using "cessation /withdrawal /discontinuation /stopping" with "anticholinergic*" or "antiparkinson*" and "neuroleptic*" or "antipsychotic*". Additional articles were obtained by searching the bibliographies of relevant references. Earlier studies of anticholinergic agent discontinuation in patients receiving first-generation antipsychotics reported relapse rates of extrapyramidal symptoms between 4% and 80%, reflecting the heterogeneity of the studies. Two recent studies of patients prescribed second-generation antipsychotics obtained relapse rates of 4% and 33%. Some studies suggest improvement in tardive dyskinesia with cessation of anticholinergics. Four studies examined the effects of anticholinergic agent discontinuation on cognition and all observed an improvement post-discontinuation. Changes in symptoms of schizophrenia with anticholinergic discontinuation are conflicting, with more recent studies suggesting an improvement. Given their questionable benefit with continued use, clinicians should consider a gradual withdrawal of anticholinergic agents in stable patients receiving antipsychotics.

  20. Anticholinergic Exposure During Rehabilitation: Cognitive and Physical Function Outcomes in Patients With Delirium Superimposed On Dementia

    PubMed Central

    Kolanowski, Ann; Mogle, Jacqueline; Fick, Donna M.; Campbell, Noll; Hill, Nikki; Mulhall, Paula; Behrens, Liza; Colancecco, Elise; Boustani, Malaz; Clare, Linda

    2015-01-01

    Objectives We examined the association between anticholinergic medication exposure and subsequent cognitive and physical function in patients with delirium superimposed on dementia during rehabilitation. We also examined length of stay and discharge disposition by anticholinergic medication exposure. Design In this secondary analysis we used control group data from an ongoing randomized clinical trial. Setting/Participants Participants with delirium and dementia were enrolled at admission to post-acute care. These 99 participants had a mean age of 86.11 (± 6.83) years; 67.6% were female; 98% were Caucasian; and 33% were positive for at least one APOE e4 allele. Measures We obtained daily measures of cognitive and physical function using: Digit Span; memory, orientation and attention items from the Montreal Cognitive Assessment; CLOX; Confusion Assessment Method; and Barthel Index. Anticholinergic medication exposure was measured weekly using the Anticholinergic Cognitive Burden Scale. Results Using multilevel models for time we found that greater use of clinically relevant anticholinergic medications in the previous week reduced cognitive and physical function, as measured by Digit Span Backwards and the Barthel Index, in the current week. There was no effect of anticholinergic medication use on delirium severity, and APOE status did not moderate any outcomes. Greater use of clinically relevant anticholinergic medications was related to longer length of stay but not discharge disposition. Conclusion For vulnerable older adults, anticholinergic exposure represents a potentially modifiable risk factor for poor attention, working memory, physical function and greater length of stay during rehabilitation. PMID:26419732

  1. Anticholinergic Toxic Syndrome Caused by Atropa Belladonna Fruit (Deadly Nightshade): A Case Report

    PubMed Central

    Demirhan, Abdullah; Tekelioğlu, Ümit Yaşar; Yıldız, İsa; Korkmaz, Tanzer; Bilgi, Murat; Akkaya, Akcan; Koçoğlu, Hasan

    2013-01-01

    Atropa Belladonna poisoning may lead to anticholinergic syndrome. Ingestion of high amounts of the plant may cause lethargy, coma, and even a serious clinical picture leading to death. In this case report, we aimed to present a case with anticholinergic syndrome that developed after ingestion of the fruit called “Deadly Nightshade” in our country. PMID:27366377

  2. Efficacy assessment of various anticholinergic agents against topical sarin-induced miosis and visual impairment in rats.

    PubMed

    Gore, Ariel; Brandeis, Rachel; Egoz, Inbal; Peri, David; Turetz, Joseph; Bloch-Shilderman, Eugenia

    2012-04-01

    Eye exposure to the organophosphorus (OP) irreversible acetylcholinesterase inhibitor sarin results in long-term miosis and reduction in visual function. Anticholinergic drugs, such as atropine or homatropine, which are used topically in order to counter these effects may produce mydriasis and partial cycloplegia, which may worsen visual performance. This study was aimed to test the efficacy of short-acting anticholinergic drugs against sarin-induced miosis and visual impairment, which will minimally insult vision. Long-Evans rats, exposed topically to various sarin doses from 0 to 10 μg, showed a dose-dependent miosis, which returned to pre-exposure levels within 24-48 h. Tropicamide treatment rapidly widened the miotic effect to a different extent depending on time following treatment and dosage given. Cyclopentolate, however, showed a delayed response that finally widened the pupils in a dose-dependent manner. Atropine treatment showed a rapid widening of the pinpoint pupils exceeding baseline level finally causing mydriasis. Light reflex test showed that the contraction ability of the iris following atropine treatment was impaired, as opposed to the use of tropicamide which facilitated the iris contraction, similar to control. Finally, tropicamide and atropine treatments ameliorated the visual impairment, as opposed to cyclopentolate, which worsened visual performance. Considering that tropicamide treatment against sarin exposure did not cause mydriasis nor did it impair the iris contraction flexibility as a response to light, the use of this drug should be taken into consideration as a first-choice topical treatment against OP intoxication.

  3. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; hide

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  4. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; Romeo, V. D.; Behl, C. R.

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  5. Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease

    PubMed Central

    Crispo, James A. G.; Willis, Allison W.; Thibault, Dylan P.; Fortin, Yannick; Hays, Harlen D.; McNair, Douglas S.; Bjerre, Lise M.; Kohen, Dafna E.; Perez-Lloret, Santiago; Mattison, Donald R.; Krewski, Daniel

    2016-01-01

    Background Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. Methods Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. Results Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge. Conclusions We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD. PMID:26939130

  6. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

    PubMed Central

    Jawaid, Talha; Jahan, Shah; Kamal, Mehnaz

    2015-01-01

    The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.]), perindopril (0.1 mg/kg b.w., [i.p.]), enalapril (0.1 mg/kg b.w., [i.p.]), and ramipril (0.1 mg/kg b.w., [i.p.]) were administered in different group of animals for 5 days. On 5th day, scopolamine (1 mg/kg b.w., i.p.) was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM) test and pole climbing test (PCT). Biochemical estimations like glutathione (GSH), malondialdehyde (MDA), and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril. PMID:26317078

  7. Distribution of hyoscyamine and scopolamine in Datura stramonium.

    PubMed

    Miraldi, E; Masti, A; Ferri, S; Barni Comparini, I

    2001-08-01

    The production of hyoscyamine and scopolamine in Datura stramonium has been investigated in the different plant parts, at different stages of their life cycle. Maximum contents were found in the stems and leaves of young plants, hyoscyamine being always the predominant component.

  8. Effects of scopolamine on autonomic profiles underlying motion sickness susceptibility

    NASA Technical Reports Server (NTRS)

    Uijtdehaage, Sebastian H. J.; Stern, Robert M.; Koch, Kenneth L.

    1993-01-01

    The purpose of this study was to examine the effects of scopolamine on the physiological patterns occurring prior to and during motion sickness stimulation. In addition, the use of physiological profiles in the prediction of motion sickness was evaluated. Sixty subjects ingested either 0.6 mg scopolamine, 2.5 mg methoscopolamine, or a placebo. Heart rate (HR), respiratory sinus arrhythmia (an index of vagal tone), and electrogastrograms were measured prior to and during the exposure to a rotating optokinetic drum. Compared to the other groups, the scopolamine group reported fewer motion sickness symptoms, and displayed lower HR, higher vagal tone, enhanced normal gastric myoelectric activity, and depressed gastric dysrhythmias before and during motion sickness induction. Distinct physiological profiles prior to drum rotation could reliably differentiate individuals who would develop gastric discomfort from those who would not. Symptom-free subjects were characterized by high levels of vagal tone and low HR across conditions, and by maintaining normal (3 cpm) electrogastrographic activity during drum rotation. It was concluded that scopolamine offered motion sickness protection by initiating a pattern of increased vagal tone and gastric myoelectric stability.

  9. Effect of residual solvent in polymer adhesive matrix on release and skin permeation of scopolamine.

    PubMed

    Anders, Kunst; Lee, Geoffrey

    2015-08-01

    The effects of varying level of residual solvent on the release and permeation of scopolamine from two different polyacrylate matrices through excised mouse skin has been determined. Matrices of the drug-in-adhesive type were prepared having different contents of residual ethyl acetate or heptane adjusted via the drying time at 30°C in a forced-convection oven. The neutral DuroTak 87-4098 showed no effects of residual ethyl acetate on either release or permeation, but was influenced by residual heptane. An increase in release rate from the matrix occurred with an enhancing effect on permeation. The self-curing DuroTak 87-2677 showed effects of residual heptane on both release and permeation. Both solvents were lost from the matrix on contact with an aqueous acceptor medium, although to different extents. Levels of residual ethyl acetate or heptane that fall below the ICH guideline (0.5% w/w) had, however, only a minor, yet measurable, effect on scopolamine release and skin uptake compared with higher solvent levels.

  10. Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

    NASA Technical Reports Server (NTRS)

    Lakshmi, Putcha; Singh, R. P.; Crady, V. A.; Derendorf, H.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  11. Scopolamine modulates paternal parental retrieval behavior in mice induced by the maternal mate.

    PubMed

    Fujimoto, Hiroko; Liu, Hong-Xiang; Lopatina, Olga; Brown, David A; Higashida, Haruhiro

    2013-06-24

    Appropriate parental care by the father can greatly facilitate healthy human family life. Much less is known from animal studies about the factors leading to paternal parental care than those favoring maternal parent care. Recently, we have reported that sires of the ICR strain of laboratory mice can express maternal-like retrieval behavior when separated from their pups through ultrasound and pheromonal signals from the dam, i.e. mate-dependent parental care. The sire's retrieval behavior was inhibited by prior treatment of scopolamine, a muscarinic cholinergic inhibitor, and recovered by physostigmine. KCNQ K(+)-channel blocking and enhancing drugs, linopiridine and retigabine, were also examined. Linopiridine alone did not enhance care after pairing with the dam, nor change scopolamine-induced inhibition of care. Retigabine totally suppressed parental care, and this effect was partially rescued by co-administration of linopiridine. These results indicate the involvement of cholinergic cellular signaling in the central nervous system in the maternal induction of paternal parental behavior in ICR mice.

  12. Effects of discontinuing anticholinergic treatment on movement disorders, cognition and psychopathology in patients with schizophrenia

    PubMed Central

    Beauclair, Linda; Annable, Lawrence; Bélanger, Marie-Claire; Kolivakis, Theodore T.; Margolese, Howard C.

    2014-01-01

    Background: Physicians have prescribed anticholinergic agents such as benztropine, procyclidine, biperiden and trihexyphenidyl for treatment and prophylaxis of antipsychotic-induced extrapyramidal symptoms (EPS) for decades. Anticholinergic agents can however worsen tardive dyskinesia and cause many adverse effects, including cognitive impairment. Previous studies of anticholinergic discontinuation in patients with schizophrenia receiving antipsychotics have yielded a wide range of EPS relapse rates. Improvement in cognition after anticholinergic withdrawal was observed in some studies. Objective: This study evaluated the effect of anticholinergic discontinuation on movement disorders, cognition and general psychopathology after a 4-week taper in 20 outpatients with schizophrenia or schizoaffective disorder treated with antipsychotics. Results: Eighteen of twenty patients successfully discontinued their anticholinergic medication; two did not because of akathisia. Repeated measures analysis of variance did not show a significant effect of anticholinergic discontinuation on total Extrapyramidal Symptoms Rating Scale score or on the Parkinsonism, Akathisia, Dystonia or Tardive Dyskinesia subscales. However, significant improvement was found on the Brief Assessment of Cognition in Schizophrenia composite z score at weeks 6, 8 and 12 compared with baseline. Significant improvements were seen on the motor and the symbol-coding tasks. No significant effects were observed on the Positive and Negative Syndrome Scale, Clinical Global Impression – Severity and Clinical Global Impression – Improvement scales. Conclusion: In this 12-week study of anticholinergic discontinuation in 20 outpatients with schizophrenia or schizoaffective disorder, gradual decrease and discontinuation of anticholinergics led to a positive effect on cognition. There were no adverse consequences on general psychopathology and no significant differences for 18 of 20 subjects on movement disorders

  13. Anticholinergic use in children and adolescents after initiation of antipsychotic therapy

    PubMed Central

    Hong, Irene S.; Bishop, Jeffrey R.

    2013-01-01

    Background Second generation antipsychotics (SGAs) are thought to have a lower likelihood of inducing extrapyramidal symptoms (EPS) than first generation antipsychotics (FGAs). Clinical observations suggest that younger patients may be more sensitive to SGA-associated EPS than adults and require therapy with anticholinergic agents, which are known to impair cognitive performance. The scope of anticholinergic use in this patient population and differences in utilization across SGAs (as well as FGAs) has not been extensively studied. Objective The primary objective of this study was to determine the proportion of patients five to 18 years of age who received anticholinergic therapy during the initial stages of antipsychotic treatment. A secondary objective was to compare anticholinergic use across patients receiving aripiprazole, risperidone, and quetiapine, SGAs previously identified to be the most commonly prescribed at the academic institution studied. Methods Patients five to 18 years of age initiating a trial of an antipsychotic between January 1, 2005 and September 1, 2008 were identified in a retrospective review of prescription and medical records. Demographic characteristics, antipsychotic and anticholinergic utilization, indications, diagnoses, and concomitant medications and doses were collected from the electronic medical record. For patients who received more than one therapeutic course of an antipsychotic during the identified timeframe, only the first course identified in the medical record was used for analyses. Anticholinergic utilization at antipsychotic initiation and after 30 days was assessed. Variables associated with anticholinergic use and differences across agents were identified. Results A total of 235 antipsychotic treatment courses were identified. Of these, 152 patients met our inclusion criteria and represented the first documented use of an antipsychotic at the present institution. Anticholinergic use at any time during the first 30

  14. Epoxidation in Vivo of Hyoscyamine to Scopolamine Does Not Involve a Dehydration Step

    PubMed Central

    Hashimoto, Takashi; Kohno, Junko; Yamada, Yasuyuki

    1987-01-01

    Hyoscyamine is epoxidized to scopolamine via 6β-hydroxyhyoscyamine in several solanaceous plants. 6,7-Dehydrohyoscyamine has been proposed to be an intermediate in the conversion of 6β-hydroxyhyoscyamine to scopolamine on the basis of the observation that this unsaturated alkaloid is converted to scopolamine when fed to a Datura scion. To determine whether a dehydration step is involved in scopolamine biosynthesis, [6-18O]6β-hydroxyhyoscyamine was prepared from l-hyoscyamine and 18O2 using hyoscyamine 6β-hydroxylase obtained from root cultures of Hyoscyamus niger L. When [6-18O]6β-hydroxyhyoscyamine was fed to shoot cultures of Duboisia myoporoides R. BR., the labeled alkaloid was converted to scopolamine which retained 18O in the epoxide oxygen. It is concluded that 6β-hydroxyhyoscyamine is converted in vivo to scopolamine without a dehydration step. PMID:16665388

  15. Transdermal scopolamine in the prevention of motion sickness - Evaluation of the time course of efficacy

    NASA Technical Reports Server (NTRS)

    Homick, J. L.; Reschke, M. F.; Degioanni, J.; Cintron-Trevino, N. M.; Kohl, R. L.

    1983-01-01

    This study evaluated the time course of efficacy of transdermal scopolamine in the prevention of motion sickness induced by exposure to coriolis stimulation in a rotating chair. We measured levels of efficacy, quantified side effects and symptoms, and determined inter- and intra-subject variability following use of transdermal scopolamine. The response to transdermal scopolamine was highly variable, although overall we recorded a 40 percent improvement in test scores 16-72 h after application of the transdermal system. This variability could not be explained solely by the levels of scopolamine present in the blood. The improvement was not due to the artifactual repression by scopolamine of selected symptoms of motion sickness. An unexpectedly high incidence of side effects was reported. It was concluded that the therapeutic use of transdermal scopolamine be evaluated individually and that individuals be cautioned that subsequent usage may not always be effective.

  16. Mental confusion associated with scopolamine patch in elderly with mild cognitive impairment (MCI).

    PubMed

    Seo, Sang Won; Suh, Mee Kyung; Chin, Juhee; Na, Duk L

    2009-01-01

    Mental confusion or delirium can occur after application of scopolamine patch. However, predisposing factors for scopolamine-induced delirium are not known. It is expected that undetected incipient dementia or mild cognitive impairment (MCI) may be prone to develop mental confusion after applying the scopolamine patch. For the past 5 years, we found seven elderly women who had experienced transdermal scopolamine-induced mental confusion. They underwent neuropsychological tests after recovery from mental confusion (mean duration from onset to the test: 66 days). The results showed that all the patients were impaired in at least one of cognitive domains, fulfilling the criteria of MCI. These findings suggest that scopolamine patch-induced mental confusion should be included in the differential diagnoses of mental confusion in elderly, especially in travel situation, and that older people with undetected MCI are prone to develop scopolamine patch-induced mental confusion.

  17. Transdermal scopolamine in the prevention of motion sickness - Evaluation of the time course of efficacy

    NASA Technical Reports Server (NTRS)

    Homick, J. L.; Reschke, M. F.; Degioanni, J.; Cintron-Trevino, N. M.; Kohl, R. L.

    1983-01-01

    This study evaluated the time course of efficacy of transdermal scopolamine in the prevention of motion sickness induced by exposure to coriolis stimulation in a rotating chair. We measured levels of efficacy, quantified side effects and symptoms, and determined inter- and intra-subject variability following use of transdermal scopolamine. The response to transdermal scopolamine was highly variable, although overall we recorded a 40 percent improvement in test scores 16-72 h after application of the transdermal system. This variability could not be explained solely by the levels of scopolamine present in the blood. The improvement was not due to the artifactual repression by scopolamine of selected symptoms of motion sickness. An unexpectedly high incidence of side effects was reported. It was concluded that the therapeutic use of transdermal scopolamine be evaluated individually and that individuals be cautioned that subsequent usage may not always be effective.

  18. Effects of scopolamine on dopamine neurons in the substantia nigra: role of the pedunculopontine tegmental nucleus.

    PubMed

    Di Giovanni, Giuseppe; Shi, Wei-Xing

    2009-08-01

    Previous neurochemical and behavioral studies suggest that muscarinic receptor antagonism has an excitatory effect on the nigrostriatal dopamine (DA) system. Using in vivo extracellular single unit recording, this study examined whether blockade of the muscarinic receptor by scopolamine alters the firing properties of DA neurons in the substantia nigra (SN). Scopolamine was administered either systemically or locally to DA neurons using microiontophoresis. Surprisingly, scopolamine did not cause any significant change in either the firing rate or pattern of the spontaneously active DA neurons. However, systemic injection of scopolamine significantly increased the number of active DA neurons in the SN. Local infusion of scopolamine into the pedunculopontine tegmental nucleus (PPT) mimicked the effect induced by systemically administered scopolamine, significantly increasing the number of active DA neurons without altering the firing rate and pattern. These results suggest that the reported increase in striatal DA release induced by scopolamine is in part mediated by activation of silent nigral DA neurons. The experiments with PPT local infusion further suggest that part of the effect of scopolamine may be due to its blockade of the inhibitory muscarinic autoreceptors on PPT cholinergic cells. The latter effect may lead to activation of quiescent DA neurons by increasing acetylcholine (ACh) release in the SN or in other brain areas providing inputs to DA neurons. Further understanding of the mechanism of action of scopolamine may help us further understand the role of ACh in both the pathophysiology and treatment of DA-related disorders including schizophrenia and Parkinson's disease.

  19. Protection against sarin-induced seizures in rats by direct brain microinjection of scopolamine, midazolam or MK-801.

    PubMed

    Skovira, Jacob W; McDonough, John H; Shih, Tsung-Ming

    2010-01-01

    Control of seizure activity is critical to survival and neuroprotection following nerve agent exposure. Extensive research has shown that three classes of drugs, muscarinic antagonists, benzodiazepines, and N-methyl-D: -aspartate antagonists, are capable of moderating these seizures. This study began to map the neural areas in rat brain that respond to these three drug classes resulting in anticonvulsant effects. Drugs of each class (scopolamine, midazolam, MK-801) were evaluated for their ability to prevent sarin-induced seizures when injected into specific brain areas (lateral ventricle, anterior piriform cortex, basolateral amygdala, area tempestas). Animals were pretreated by microinjection with saline or a dose of drug from one of the three classes 30 min prior to receiving 150 microg/kg sarin, subcutaneously, followed by 2.0 mg/kg atropine methylnitrate, intramuscularly. Animals were then returned to their cages, where electroencephalographic activity was monitored for seizures. Anticonvulsant effective doses (ED(50)) were determined using an up-down dosing procedure over successive animals. Scopolamine provided anticonvulsant effects in each area tested, while midazolam was effective in each area except the lateral ventricle. MK-801 was only effective at preventing seizures when injected into the basolateral amygdala or area tempestas. The results show a unique neuroanatomical and pharmacological specificity for control of nerve agent-induced seizures.

  20. AUGS Consensus Statement: Association of Anticholinergic Medication Use and Cognition in Women With Overactive Bladder.

    PubMed

    Overactive bladder affects a significant portion of the overall population and has substantial impact on daily activities and quality-of-life. When considering treatment, behavioral therapies should be instituted first, followed by medical therapies. Anticholinergic medications and beta-3 agonists are often used as initial pharmacologic therapy, but caution should be taken in prescribing anticholinergic medications in frail or cognitively impaired patients. Recently, concerns have developed regarding anticholinergic medications and the associated risk of cognitive impairment, dementia, and Alzheimer disease in the general population. Given the available evidence, which has shown significant associations between anticholinergic medication use and increased risk of cognitive impairment and dementia, providers should counsel on the associated risks, prescribe the lowest effective dose, and consider alternative medications in patients at risk.

  1. Induction of a transient dysexecutive syndrome in Parkinson's disease using a~subclinical dose of scopolamine.

    PubMed

    Bédard, M.A.; Lemay, S.; Gagnon, J.F.; Masson, H.; Paquet, F.

    1998-01-01

    Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome (SCFS) that is mainly characterized by executive dysfunctions. The complete biochemistry of these dysfunctions remain misunderstood although many studies have suggested a role of the dopaminergic lesions. However, cholinergic lesions in this disease may also account for the SCFS occurrence. The present study has assessed the effects of an acute subclinical dose of scopolamine in normal controls and in PD patients who were devoid of cognitive deficit. Results indicates that PD patients but not normal controls developed a transient SCFS for the duration of the drug action. In contrast to other populations with cholinergic depletions - such as Alzheimer's disease - cholinergic blockage in PD exacerbates specifically the dysexecutive syndrome without inducing amnesia or sedation. Such a discrepancy between these two neuropsychological profiles are discussed in terms of the specificity of the underlying cholinergic lesions.

  2. Urodynamic approach to female urinary incontinence refractory to treatment with anticholinergics.

    PubMed

    Naranjo-Ortiz, Cristina; Clemente-Ramos, Luis Miguel; Salinas-Casado, Jesús; Méndez-Rubio, Santigo

    2012-12-01

    The administration of empirical anticholinergic treatment is widespread in women with urinary incontinence and has produced varied results. The objective of our paper is to determine the effectiveness of anticholinergics for the treatment of female urinary incontinence and to determine by urodynamics the possible causes that may explain the resistance to anticholinergics to obtain urodynamic predictors of success or failure. We evaluated 182 women over 14 years of age with urinary incontinence that had previously been treated with anticholinergics for at least three months. The patients underwent a complete medical history including clinical history, physical examination, and urodynamic and lower urinary tract video-radiologic studies. Statistical analysis was performed using SPSS 17.0 for Windows. Clinical therapeutic efficacy was demonstrated in 39.6% of cases. Cystometric bladder capacity was decreased in 89.2%of patients that did not improve clinically with anticholinergics (p=0.01). Detrusor overactivity was urodynamically demonstrated in 51% of cases (p=0.05) among patients without clinical improvement with anticholinergic treatment. This hyperactivity was demonstrated during early bladder filling (<100ml). Urodynamic stress urinary incontinence (SUI) was demonstrated in 26.5% of patients without clinical improvement after treatment (p=0.04). Lower urinary tract obstruction was urodynamically demonstrated in 20.6% of patients with no clinical improvement (p=0.05). Urodynamic data did not demonstrate a relationship between detrusor overactivity, a high-grade cystocele ( 37.4% of total), and irregular bladder morphology (11.5% of total). It is important to conduct urodynamic study before starting anticholinergic treatment of females with urinary incontinence to identify therapeutic data of poor prognosis, such as SUI and lower urinary tract obstruction, thus optimizing the therapeutic efficacy of anticholinergics.

  3. The Cognitive Cost of Anticholinergic Burden: Decreased Response to Cognitive Training in Schizophrenia

    PubMed Central

    Vinogradov, Sophia; Fisher, Melissa; Warm, Heather; Holland, Christine; Kirshner, Margaret A.; Pollock, Bruce G.

    2013-01-01

    Objective Schizophrenia is treated with medications that raise serum anticholinergic activity and are known to adversely affect cognition. The authors examined the relationship between serum anticholinergic activity and baseline cognitive performance and response to computerized cognitive training in outpatients with schizophrenia. Method Fifty-five patients were randomly assigned to either computerized cognitive training or a computer games control condition. A neurocognitive battery based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was performed at baseline and after the intervention. Serum anticholinergic activity, measured at study entry by radioreceptor assay, was available for 49 patients. Results Serum anticholinergic activity showed a significant negative correlation with baseline performance in verbal working memory and verbal learning and memory, accounting for 7% of the variance in these measures, independent of age, IQ, or symptom severity. Patients in the cognitive training condition (N=25) showed a significant gain in global cognition compared to those in the control condition, but this improvement was negatively correlated with anticholinergic burden. Serum anticholinergic activity uniquely accounted for 20% of the variance in global cognition change, independent of age, IQ, or symptom severity. Conclusions Serum anticholinergic activity in schizophrenia patients shows a significant association with impaired performance in MATRICS-based measures of verbal working memory and verbal learning and memory and is significantly associated with a lowered response to an intensive course of computerized cognitive training. These findings underscore the cognitive cost of medications that carry a high anticholinergic burden. The findings also have implications for the design and evaluation of cognitive treatments for schizophrenia. PMID:19570929

  4. Release and Skin Permeation of Scopolamine From Thin Polymer Films in Relation to Thermodynamic Activity.

    PubMed

    Kunst, Anders; Lee, Geoffrey

    2016-04-01

    The object was to demonstrate if the diffusional flux of the drug out of a drug-in-adhesive-type matrix and its subsequent permeation through an excised skin membrane is a linear function of the drug's thermodynamic activity in the thin polymer film. The thermodynamic activity, ap(*), is defined here as the degree of saturation of the drug in the polymer. Both release and release/permeation of scopolamine base from 3 different poylacrylate pressure-sensitive adhesives (PSAs) were measured. The values for ap(*) were calculated using previous published saturation solubilities, wp(s), of the drug in the PSAs. Different rates of release and release/permeation were determined between the 3 PSAs. These differences could be accounted for quantitatively by correlating with ap(*) rather than the concentration of the drug in the polymer films. At similar values for ap(*) the same release or release/permeation rates from the different polymers were measured. The differences could not be related to cross-linking or presence of ionizable groups of the polymers that should influence diffusivity.

  5. Decaffeinated coffee prevents scopolamine-induced memory impairment in rats.

    PubMed

    Jang, Young Jin; Kim, Jiyoung; Shim, Jaesung; Kim, Chang-Yul; Jang, Jung-Hee; Lee, Ki Won; Lee, Hyong Joo

    2013-05-15

    Several human studies have reported that coffee consumption improves cognitive performance. In the present study, we investigated whether instant decaffeinated coffee also ameliorates cognitive performance and attenuates the detrimental effects of scopolamine on memory. Memory performance was evaluated in Morris water maze test and passive avoidance test. Instant decaffeinated coffee (p.o.) at 120 or 240 mg/kg in Sprague-Dawley rats, which is equivalent to approximately three or six cups of coffee, respectively, in a 60 kg human, was administered for two weeks. Oral gavage administration of instant decaffeinated coffee inhibited scopolamine-induced memory impairment, which was measured by Morris water maze test and passive avoidance test. Instant decaffeinated coffee suppressed scopolamine-mediated elevation of tumor necrosis factor-α (TNF-α) and stimulation of nuclear factor-κB (NF-κB) pathway (i.e., phosphorylation of IκBα and p65) in the rat hippocampus. These findings suggest that caffeine-free decaffeinated coffee may prevent memory impairment in human through the inhibition of NF-κB activation and subsequent TNF-α production. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. [Risk/benefit assessment in the treatment of Alzheimer's disease. Drug interactions].

    PubMed

    Hernández-Arroyo, María Jesús; Díaz-Madero, Alfonso

    2016-01-01

    Anticholinergic drugs reduce the efficacy of acetylcholinesterase inhibitors (AChEI) and are inappropriate in elderly patients. The aim of this study is to determine the prevalence rate of prescription AChEI drugs and anticholinergics in a Healthcare Area, to identify the affected patients, and to inform the attending physicians, in order to evaluate the suitability of treatments. A descriptive cross-sectional observational study of prevalence. Patients on treatment with AChEI and any anticholinergic drug in the first quarter of 2015 were selected. The review of Duran et al. was used as reference to identify anticholinergics, assigning a score to each drug according to its anticholinergic potency. Physicians were provided with a report about the interaction, the list of affected patients, and recommendations. A total of 486 patients were included in the study, representing 59.0% of total patients with Alzheimer's disease in the Area. There were 66.0% women, and 86.8% of the patients were older than 75 years, and with a mean of 9.2 drugs per patient. The mean number of anticholinergic drugs was 1.6, and 38.3% of patients were prescribed various anticholinergic drugs, with 23.9% on high potency anticholinergic drugs. A statistically significant association was found between taking an anticholinergic and AChEI concomitantly (P=.000; OR: 3.9). The prevalence of interactions between AChEI and anticholinergic drugs is relevant, considering that it affects vulnerable members of the population. Providing physicians with information about the interaction could help them make clinical decisions, and could improve patient safety, as well as health outcomes. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Aprohrne and Scopolamine: Metabolic and Clinical Chemical Effects during Exercise

    DTIC Science & Technology

    1989-05-17

    as well as thermoregulation (1,2,12). In fact, in a recent report we have compared the increments in core temperature of sedentary heat- stressed ...EXERCISECONTROL I AMIDOE IOEN AT 20-C ON Cit.ULATING LEVELS OF SODIUM. POTASSIUM. AND LACTATESCOPOLAMINE APROPHEN ________ ___ ___ LOW DOSE LOW DOSE...the effects of this anticholinergic on heating rate in a sedentary, heat- stressed rat model. Freireich et al. (5) had earlier hypothesized that an

  8. Post-training scopolamine treatment induced maladaptive behavior in open field habituation task in rats.

    PubMed

    Popović, Natalija; Caballero-Bleda, María; Popović, Miroljub

    2014-01-01

    The effects of scopolamine on memory consolidation are controversial and depend on several factors (i.e. site of administration, time of administration and testing, dose, cognitive task, experimental protocol, specie, strain, etc.). Generally, the range dose of systemic administered scopolamine, used in memory consolidation studies, has varied from 0.05 to 50 mg/kg. However, according to the literature, the most frequently used doses of scopolamine efficient on memory consolidation, are 1 and 30 mg/kg, low and high doses, respectively. In open field habituation studies only lower doses of scopolamine were used to test memory consolidation. Therefore, in the present study we compared the effects of low (1 mg/kg) and high (30 mg/kg) scopolamine dose, on the open field habituation task, in male Wistar rats. Scopolamine was administered immediately after the acquisition task and animals were retested 48 h later on. On the retested day, the ambulation and rearing in the open field decreased in the same manner in all tested groups. In saline- and 1 mg/kg scopolamine-treated animals, the time spent in grooming significantly decreased in the habituation task, while the same parameter significantly increased in animals treated with 30 mg/kg of scopolamine. The defecation rate significantly decreased (control group), maintained (1 mg/kg of scopolamine treated animals) or significantly increased (30 mg/kg of scopolamine treated group) on retention test. In conclusion, the present data suggest that post-training scopolamine administration does not affect locomotion neither exploration in the habituation to a novel environment, but increases defecation and grooming, two behaviours associated with fearful and stressful situations.

  9. Time course of scopolamine effect on memory consolidation and forgetting in rats.

    PubMed

    Popović, Miroljub; Giménez de Béjar, Verónica; Popović, Natalija; Caballero-Bleda, María

    2015-02-01

    The effect of scopolamine on the consolidation and forgetting of emotional memory has not been completely elucidated yet. The aim of the present study was to investigate the time course of scopolamine effect on consolidation and forgetting of passive avoidance response. In a first experiment of the present study, we tested the effect of scopolamine (1mg/kg, i.p., immediately after acquisition), on 24h and 48h retention performance of the step-through passive avoidance task, in adult male Wistar rats. On the 24h retested trial, the latency of the passive avoidance response was significantly lower, while on the 48h retested trial it was significantly higher in scopolamine than in the saline-treated group. In a second experiment, we assessed the 24h time course of scopolamine (1mg/kg) effect on memory consolidation in passive avoidance task. We found that scopolamine administration only within the first six and half hours after acquisition improved memory consolidation in 48h retention performance. Finally, a third experiment was performed on the saline- and scopolamine-treated rats (given immediately after acquisition) that on the 48h retention test did not step through into the dark compartment during the cut-off time. These animals were retested weekly for up to first three months, and after that, every three months until the end of experiment (i.e., 15 months after acquisition). The passive avoidance response in the saline treated group lasted up to 6 weeks after acquisition, while in the scopolamine treated group 50% of animals conserved the initial level of passive avoidance response until the experiment end point. In conclusion, the present data suggest that (1) improving or impairment effect of scopolamine given in post-training periods depends on delay of retention trial, (2) memory consolidation process could be modify by scopolamine within first six and half hours after training and (3) scopolamine could delay forgetting of emotional memory.

  10. Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes.

    PubMed

    Boudreau, Denise M; Yu, Onchee; Gray, Shelly L; Raebel, Marsha A; Johnson, Jeanene; Larson, Eric B

    2011-11-01

    To determine the extent of concomitant use of cholinesterase inhibitor (ChI) and anticholinergic (ACh) medications and the clinical consequences of dual use in a population-based setting. Retrospective cohort study. Group Health Cooperative and Kaiser Permanente Colorado. Five thousand six hundred twenty-five adults aged 50 and older who began new use of a ChI between 2000 and 2007. Rates and characteristics of concomitant ChI and ACh use and the association between dual use and the outcomes of death and nursing home placement (claim from a nursing home with no prior claims used as a proxy). Thirty-seven percent of ChI users also received AChs. Eleven percent of ChI users were concomitantly using two or more moderate to potent AChs. Median duration of this concomitant use was approximately 4 months, but a substantial proportion (25%) continued to use both medication classes simultaneously for longer than 12 months. In 23% of ChI users, AChs were being used at the time ChI therapy was initiated. The majority of this ACh use (77%) was not stopped once ChIs were started. No association was observed between concomitant use and risk of death or nursing home placement. These results should raise awareness about the prevalence and potential inappropriateness of concomitant use of ChIs and AChs and promote evaluations of practices intended to improve care standards. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

  11. Dry eye findings worsen with anticholinergic therapy in patients with urge incontinence.

    PubMed

    Ozen Tunay, Zuhal; Ozdemir, Ozdemir; Ergintürk Acar, Damla; Cavkaytar, Sabri; Ersoy, Ebru

    2016-06-01

    To evaluate the effects of oral anticholinergic (OAC) drugs on tear secretion in women with overactive bladder over a 3-month follow-up period. In this prospective study, 108 women with a diagnosis of overactive bladder were evaluated. All patients were examined ophthalmologically at baseline (day 0), and after 1 month (day 30) and 3 months (day 90) of OAC treatment. Tear film break-up time (BUT) and Schirmer 1 test results were recorded. The subjective complaints of the patients including dry mouth, and burning, dryness and foreign body sensation in the eyes, were also recorded. The chi-squared test or the paired sample t test as appropriate, was used for statistical analysis. The mean age of the patients was 51.8 ± 9.2 years (30 - 69 years). The most frequent subjective complaints were dry mouth and dry eyes and both complaints were significant on both day 30 and day 90. Both tear film BUT and Schirmer 1 test results were significantly lower on day 30 and day 90. Dry eye measurement values worsened with prolongation of OAC treatment (p = 0.037 and p = 0.012 for BUT, and p = 0.046 and p = 0.035 for Schirmer 1 test, on day 30 and day 90, respectively). OAC treatment in women with overactive bladder significantly and progressively affects tear secretion.

  12. Influence of benzodiazepine tranquilizers on scopolamine-induced locomotor stimulation in mice.

    PubMed

    Sansone, M

    1980-01-01

    Four benzodiazepine tranquilizers have been tested, alone or in combination with scopolamine, on the spontaneous locomotor activity of BALB/c mice. Scopolamine-induced locomotor stimulation was enhanced by chlordiazepoxide, diazepam, and medazepam, but not by bromazepam. These effects are similar to those exerted by the four benzodiazepines on amphetamine-induced locomotor stimulation and allow the same differentiation between the four derivatives.

  13. Protective effects of aerosolized scopolamine against soman-induced acute respiratory toxicity in guinea pigs.

    PubMed

    Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Song, Jian; Oguntayo, Samuel; Morthole, Venee; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2011-12-01

    The protective efficacy of the antimuscarinic agent scopolamine was evaluated against soman (o-pinacolyl methylphosphonofluoridate [GD])-induced respiratory toxicity in guinea pigs. Anesthetized animals were exposed to GD (841 mg/m(3)) by microinstillation inhalation exposure and treated 30 seconds later with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 hours. Treatment with scopolamine significantly increased survival and reduced clinical signs of toxicity and body weight loss in GD-exposed animals. Analysis of bronchoalveolar lavage (BAL) fluid showed normalization of GD-induced increased cell death, total cell count, and protein following scopolamine treatment. The BAL fluid acetylcholinesterase and butyrylcholinesterase levels were also increased by scopolamine treatment. Respiratory dynamics parameters were normalized at 4 and 24 hours post-GD exposure in scopolamine-treated animals. Lung histology showed that scopolamine treatment reduced bronchial epithelial and subepithelial inflammation and multifocal alveolar septal edema. These results suggest that aerosolized scopolamine considerably protects against GD-induced respiratory toxicity.

  14. Cognitive enhancing of pineapple extract and juice in scopolamine-induced amnesia in mice

    PubMed Central

    Momtazi-borojeni, Amir Abbas; Sadeghi-Aliabadi, Hojjat; Rabbani, Mohammed; Ghannadi, Alireza; Abdollahi, Elham

    2017-01-01

    The objective of the present study was to evaluate the cognitive enhancing of pineapple juice and ethanolic extract in scopolamine-induced cognitive deficit mice. The ethanolic extract of pineapple (Ananas comosus (L.) Merr.) was prepared by maceration method and its juice was obtained by a homogenizer. Object recognition task was used to evaluate the mice memory. Exploration time in the first and second trial was recorded. The differences in exploration time between a familiar and a novel object in the second trial were taken as a memory index. Animals were randomly assigned into 15 groups of 6 each including: control group (normal saline + vehicle), positive control group (scopolamine + rivastigmine), seven experimental groups (received scopolamine alone or scopolamine + ethanolic extract of pineapple in different doses), six other experimental groups were treated by ethanolic extract or juice of pineapple in different doses. Scopolamine (100 μL, 1 mg/kg, i.p.) and pineapple juice or extract (50, 75 and 100 mg/kg, i.p.) were administered 40 and 30 min before starting the second trial in the experimental groups. Object discrimination was impaired after scopolamine administration. Results showed that juice and ethanolic extract of pineapple significantly restored object recognition ability in mice treated with scopolamine. These finding suggested that pineapple had a protective role against scopolamine-induced amnesia, indicating its ability in management of cognitive disorders. PMID:28626484

  15. 78 FR 52939 - Prospective Grant of Exclusive Patent License: Use of Scopolamine to Treat Depression

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ... 25, 2005, titled ``Scopolamine for the Treatment of Depression and Anxiety'' [HHS Ref. No. E-175-2004... Treatment of Depression and Anxiety'' [HHS Ref. No. E-175-2004/0-EP-03]; 3. German Patent 1896025, issued December 28, 2011, titled ``Scopolamine for the Treatment of Depression and Anxiety'' [HHS Ref. No....

  16. Heart-rate variability (HRV) in the ECG trace of routine EEGs: fast monitoring for the anticholinergic effects of clozapine and olanzapine?

    PubMed

    Eschweiler, G W; Bartels, M; Längle, G; Wild, B; Gaertner, I; Nickola, M

    2002-05-01

    Drug monitoring in psychiatry usually serves psychoactive drug plasma concentration measurement. Anticholinergic properties offer a faster approach to monitoring pharmacodynamic intraindividual effects of the drug by measuring their effects on heart rate variability (HRV), which is sympathetically and parasympathetically controlled via cholinergic synapses. The plasma concentrations of the atypical antipsychotics clozapine and olanzapine correlated with parameters of HRV in 59 patients suffering from schizophrenia or schizoaffective disorder. HRV during 4 minutes at rest was extracted from the ECG trace of a routine digital EEG registration in addition to blood sampling for plasma concentration measurement (HPLC method). We calculated sympathetically and parasympathetically controlled heart frequency bands (low, medium and high frequency) and other HRV parameters, coefficient of variation (CV), and root mean square of successive differences (RMSSD). All HRV parameters were significantly more impaired in clozapine patients (n = 33, mean clozapine plasma concentration 331 +/- 294 ng/ml) than in olanzapine patients (n = 26, mean olanzapine plasma concentration 42 +/- 32 ng/ml) and demonstrated 1.7 - 4.8 times the cardiac anticholinergic properties of clozapine in vivo. 14 out of 14 patients with a CV beyond 3.2 % had clozapine plasma concentrations below the proposed optimal therapeutic concentration of 350 ng/ml. All HRV parameters were inversely and significantly correlated with the clozapine plasma concentrations (such as lgCV: r = - 0.73, p < 0.001) and, to a lesser extent, with the olanzapine plasma concentrations (lgCV r = - 0.44, p < 0.05). These results underline the potential clinical value of HRV parameter extraction from routine ECGs in predicting plasma concentrations and objective individual neurocardiac effects of drugs with anticholinergic properties.

  17. DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice.

    PubMed

    Lian, Wenwen; Fang, Jiansong; Xu, Lvjie; Zhou, Wei; Kang, De; Xiong, Wandi; Jia, Hao; Liu, Ai-Lin; Du, Guan-Hua

    2017-03-06

    Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer's disease.

  18. Distinguishing between attentional and amnestic effects in information processing: the separate and combined effects of scopolamine and nicotine on verbal free recall.

    PubMed

    Rusted, J; Eaton-Williams, P

    1991-01-01

    An important issue in our understanding of cholinergic modulation of information processing is the extent to which drug-induced changes affect memory processes per se or simply the attentional processes required for effective acquisition of information. In this study, we examined the separate and combined effects of scopolamine and nicotine on verbal free recall. A single dose of nicotine improved recall performance on supraspan lists (30 words), but not on short lists (10 words). The same dose of nicotine had no effect on the scopolamine-induced recall deficits observed for both 30 and 10 word lists. The results are discussed in terms of the independence of attention and memory processes and the specificity of action of these two cholinergic compounds.

  19. Transdermal scopolamine and perioperative anisocoria in craniofacial surgery: a report of 3 patients.

    PubMed

    Lee, David T; Jenkins, Nelson L; Anastasopulos, Alexandra J; Volpe, A George; Lee, Bernard T; Lalikos, Janice F

    2013-03-01

    Postoperative nausea and vomiting (PONV) is a common complaint after plastic and reconstructive surgery. Transdermal scopolamine is a commonly used agent for prevention of PONV. Anisocoria from transdermal scopolamine use is an adverse effect that has not been reported in the plastic surgery literature. We present a series of 3 craniofacial patients in which ipsilateral mydriasis occurred and spontaneously resolved after removal of the scopolamine patch. Given the various causes and potentially grave implications of unilateral mydriasis, we discourage the use of transdermal scopolamine in craniofacial surgery, and especially in orbital surgery. However, if transdermal scopolamine is decided to be used for PONV prophylaxis, we recommend educating the patient, the operating room staff, and the surgical team regarding this potential adverse effect and to avoid finger-to-eye contamination after patch manipulation.

  20. Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

    PubMed

    Choi, Mi-Ran; Lee, Min Young; Hong, Ji Eun; Kim, Jeong Eun; Lee, Jae-Yong; Kim, Tae Hwan; Chun, Jang Woo; Shin, Hyun Kyung; Kim, Eun Ji

    2014-10-01

    The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

  1. Perspectives on transdermal scopolamine for the treatment of postoperative nausea and vomiting.

    PubMed

    Pergolizzi, Joseph V; Philip, Beverly K; Leslie, John B; Taylor, Robert; Raffa, Robert B

    2012-06-01

    Transdermal scopolamine, a patch system that delivers 1.5 mg of scopolamine gradually over 72 hours following an initial bolus, was approved in the United States in 2001 for the prevention of postoperative nausea and vomiting (PONV) in adults. Scopolamine (hyoscine) is a selective competitive anatagonist of muscarinic cholinergic receptors. Low serum concentrations of scopolamine produce an antiemetic effect. Transdermal scopolamine is effective in preventing PONV versus placebo [relative risk (RR)=0.77, 95% confidence interval (CI), 0.61-0.98, P = 0.03] and a significantly reduced risk for postoperative nausea (RR=0.59, 95% CI, 0.48-0.73, P < 0.001), postoperative vomiting (RR=0.68, 95% CI, 0.61-0.76, P < 0.001), and PONV (RR 0.73, 95% CI, 0.60-0.88, P = 001) in the first 24 hours after the start of anesthesia.

  2. Some structure activity relationships of phencyclidine derivatives as anticholinergic agents in vitro and in vivo.

    PubMed

    Maayani, S; Weinstein, H

    1979-01-01

    Phencylidine derivatives exhibit multiple interactions with cholinergic systems: they block nicotinic and muscarinic receptors,and inhibit both acetyl and butyrylcholinesterase. In peripheral tissue, the net pharmacological effects of the phencyclidines is antiacetylcholine activity. The dissociation constants measured in isolated smooth muscle and from competition experiments for the muscarinic high-affinity binding sites in brain homogenates (Kd = 10(-5) - 10(-6) M) are 3--4 orders of magnitude lower than those of anticholinergic glycolate esters. However, phencyclidines have comparable potency to that of d-tubocurarine in blocking the nicotinic receptor in the isolated frog rectus abdominis (Kd = 10(-6) M). Brain uptake experiments of (3H) labeled phencyclidine showed that during the time period in which central effects are observed with these drugs their concentration in brain reaches values close to the Kd (10(-5) - 10(-6) M). This finding, and the cross tolerance observed in vivo between phencyclidine and other centrally acting cholinergic drugs supports the possible involvement of cholinergic interactions in the psychotropic action of phenyclidine derivatives. Quantum chemical calculations of the interaction pharmacophores of drugs in the phencyclidine series have indicated the molecular determinants for the interaction of these drugs with the muscarinic receptor. The calculations revealed that these drugs can match the reactivity characteristics of ACh and the semi-rigid muscarinic agonist 3-acetoxyquinuclidine, but their rigid molecular frame will be conductive to antagonistic rather than agonistic activity when the drug-receptor complex is formed. The identification of a "cholinergic interaction pharmacophore" for these drugs by quantum mechanical calculations made possible the suggestion of other active phencyclidine derivatives, e.g. p-NH2 and p-OH analogs which proved to be equipotent to phencyclidine. The inactivity of the p-NO2 derivative was also

  3. 21 CFR 310.533 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as an...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... hay fever, allergy, rhinitis, and the common cold. Atropine sulfate for oral use as an anticholinergic... offered over-the-counter (OTC) for human use as an anticholinergic in cough-cold drug products. 310.533... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as...

  4. 21 CFR 310.533 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as an...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... hay fever, allergy, rhinitis, and the common cold. Atropine sulfate for oral use as an anticholinergic... offered over-the-counter (OTC) for human use as an anticholinergic in cough-cold drug products. 310.533... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as...

  5. 21 CFR 310.533 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as an...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... hay fever, allergy, rhinitis, and the common cold. Atropine sulfate for oral use as an anticholinergic... offered over-the-counter (OTC) for human use as an anticholinergic in cough-cold drug products. 310.533... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as...

  6. 21 CFR 310.533 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as an...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... hay fever, allergy, rhinitis, and the common cold. Atropine sulfate for oral use as an anticholinergic... offered over-the-counter (OTC) for human use as an anticholinergic in cough-cold drug products. 310.533... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as...

  7. 21 CFR 310.533 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as an...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... hay fever, allergy, rhinitis, and the common cold. Atropine sulfate for oral use as an anticholinergic... offered over-the-counter (OTC) for human use as an anticholinergic in cough-cold drug products. 310.533... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as...

  8. Relative bioavailability of scopolamine dosage forms and interaction with dextroamphetamine.

    PubMed

    Boyd, Jason L; Du, Brian; Vaksman, Zalman; Locke, James P; Putcha, Lakshmi

    2007-07-01

    The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) alone and in combination with dextoamphetamine (DEX) to treat motion sickness symptoms during DC-9 parabolic flights. The medications are sometimes dispensed as custom dosage forms in gelatin capsules for convenience. Reports of treatment failure during flights by the flight surgeons suggest that these formulations may be less efficacious for the treatment of motion sickness due to unreliable and inadequate bioavailability. We estimated bioavailability of four different oral formulations used by the NASA RGO physicians for the treatment of motion sickness.

  9. Catecholaminergic responses to stressful motion stimuli, scopolamine plus amphetamine, and dexamethasone

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Chelen, W. E.

    1992-01-01

    Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.

  10. Enduring amnesia induced by ICV scopolamine is reversed by sesame oil in male rats.

    PubMed

    Tabari, Shabnam-Sadat Seyedi; Babri, Shirin; Mirzaie, Fariba; Farajdokht, Fereshteh; Mohaddes, Gisou

    2016-08-01

    To evaluated the long-term effect of scopolamine and sesame oil on spatial memory. Memory impairment induced by Intracerebroventricular (ICV) injection of scopolamine hydrochloride (10 μg/ rat). Animals were gavaged for 4 weeks with saline, sesame oil (0.5, 1, or 2 mL/kg/day), or 3 weeks with memantine (30 mg/kg/day) in advance to induction of amnesia. Morris water maze (MWM) test was conducted 6 days after microinjection of scopolamine. Then, blood and brain samples were collected and evaluated for the malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and total antioxidant status (TAS) and ferric reducing ability of plasma (FRAP). Scopolamine significantly decreased traveled distance and time spent in target quadrant in probe test. Pretreatment of rats with sesame oil (0.5 mg/kg) mitigated scopolamine-induced behavioral alterations. Measurement of MDA, SOD, and GPX in brain tissue, and FRAP and TAS in blood showed little changes in animals which had received scopolamine or sesame oil. Intracerebroventricular injection of scopolamine has a residual effect on memory after six days. Sesame oil has an improving effect on spatial memory; however this effect is possibly mediated by mechanisms other than antioxidant effect of sesame oil.

  11. Scopolamine-induced convulsions in fasted animals after food intake: sensitivity of C57BL/6J mice and Sprague-Dawley rats.

    PubMed

    Enginar, Nurhan; Nurten, Asiye; Türkmen, Aslı Zengin; Çağla, Büyüklü

    2015-05-01

    Food intake triggers convulsions in fasted BALB/c mice and Wistar albino rats treated with antimuscarinic drugs, scopolamine or atropine. Inbred strain studies have yielded considerable information regarding genetic influences on seizure susceptibility and factors contribute to epileptogenesis in rodents. This study, therefore, investigated sensitivity to antimuscarinic-induced seizures in C57BL/6J mice and Sprague-Dawley rats. Food deprivation for 48h in mice and 52h in rats did not produce strain differences in body weight loss. Fasted animals treated i.p. with 3mg/kg scopolamine developed convulsions after food intake. The incidence of convulsions was indifferent in comparison to BALB/c mice and Wistar albino rats. Number of animals developing stage 5 was more and onset of convulsions was longer in C57BL/6J mice than in BALB/c mice. Strain-related differences in sensitivity to seizures in C57BL/6J mice may need further evaluation for investigating genetic influences on scopolamine-induced seizures.

  12. A neuroanatomical analysis of the effects of a memory impairing dose of scopolamine in the rat brain using cytochrome c oxidase as principle marker.

    PubMed

    Hescham, Sarah; Temel, Yasin; Casaca-Carreira, João; Arslantas, Kemal; Yakkioui, Youssef; Blokland, Arjan; Jahanshahi, Ali

    2014-09-01

    Acetylcholine plays a role in mnemonic and attentional processes, but also in locomotor and anxiety-related behavior. Receptor blockage by scopolamine can therefore induce cognitive as well as motor deficits and increase anxiety levels. Here we show that scopolamine, at a dose that has previously been found to affect learning and memory performance (0.1 mg/kg i.p.), has a widespread effect on cytochrome c oxidase histochemistry in various regions of the rat brain. We found a down-regulation of cytochrome c oxidase in the nucleus basalis, in movement-related structures such as the primary motor cortex and the globus pallidus, memory-related structures such as the CA1 subfield of the hippocampus and perirhinal cortex and in anxiety-related structures like the amygdala, which also plays a role in memory. However choline acetyltransferase levels were only affected in the CA1 subfield of the hippocampus and both, choline acetyltransferase and c-Fos expression levels were decreased in the amygdala. These findings corroborate strong cognitive behavioral effects of this drug, but also suggest possible anxiety- and locomotor-related changes in subjects. Moreover, they present histochemical evidence that the effects of scopolamine are not ultimately restricted to cognitive parameters.

  13. Unique Scopolamine Withdrawal Syndrome After Standard Transdermal Use.

    PubMed

    Manno, Maurizio; Di Renzo, Gianfranco; Bianco, Pasquale; Sbordone, Carmine; De Matteis, Francesco

    2015-01-01

    We report the case of a 62-year-old woman who developed a withdrawal syndrome after using a standard 1.5-mg transdermal scopolamine (TDS) patch behind the ear to prevent motion sickness during sailing. The patient, who had used TDS occasionally for years without significant adverse effects, more recently, having worn a patch continuously for 7 days, approximately 24 to 36 hours after removing the patch developed dizziness, nausea, sweating, fatigue, and drowsiness. All symptoms disappeared without therapy in about 2 days. Approximately 1 year after the first episode, though, a very similar, more severe disabling reaction developed on 2 occasions. Drowsiness and malaise were accompanied by severe asthenia, orthostatic sweating, inability to stand, and hypotension. All clinical tests (electrocardiogram; spirometry; blood cell count; plasma levels of cortisol, sodium, and potassium; and liver and kidney function tests) were negative, and symptoms disappeared slowly, after several days. Although we are certain that scopolamine was responsible for the symptoms, we are less clear as to the nature of the disorder. The effects being more severe after a more prolonged use of the TDS patch, the increase in severity each successive time, and the time lag between removing the patch and appearance of symptoms all indicated a withdrawal syndrome for which several mechanisms may be suggested.

  14. Treatment of disorders characterized by reversible airway obstruction in childhood: are anti-cholinergic agents the answer?

    PubMed

    Quizon, Annabelle; Colin, Andrew A; Pelosi, Umberto; Rossi, Giovanni A

    2012-01-01

    Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from parasympathetic nerves in lungs is induced by a variety of stimuli and downregulated by the inhibitory activity of neuronal M2 muscarinic receptors via a feedback mechanism. Increased parasympathetic nerve activity occurs in a variety of airway diseases in childhood, including viral-induced wheeze and asthma. Common to these conditions are reversible airway obstruction, mucus hypersecretion, vasodilation and enhanced vascular permeability. In animal models of airway hyperreactivity similar findings of increased acetylcholine release resulting in enhanced supply of this neurotransmitter to the postjunctional smooth muscles, submucosal glands and airway vessels, were demonstrated. While the number and function of postjunctional muscarinic receptors in the airways are unchanged in such airway disorders, inhibitory activity on the parasympathetic nerves appears to be impaired. Specifically, M2 muscarinic receptor dysfunction has been demonstrated in models of bronchial hyperreactivity induced by a variety of triggers, including viruses, atmospheric pollutants and allergens. The mechanisms leading to impairment of neuronal M2 muscarinic receptor function and their putative relevance to the pathogenesis and the treatment of airway disease in childhood are described. Finally, the available data on the activity of ipratropium bromide, a short-acting anticholinergic drug, in the most common pediatric airway disease are reported and the possible therapeutic efficacy of tiotropium bromide, a more recently introduced long-acting, selective anticholinergic compound, is discussed.

  15. Lack of anticholinergic side effects with a new antidepressent--trazodone.

    PubMed

    Gershon, S; Newton, R

    1980-03-01

    An analysis was made of the occurrence of anticholinergic side effects in 15 multicenter studies of 379 patients with endogenous depression who received either trazodone, imipramine, or placebo. The incidence of 4 anticholinergic side effects was examined: dry mouth, blurred vision, bowel movement disturbance, and delayed urine flow. When the number of patients having each of the 4 symptoms was compared, there were no statistically significant differences in the incidence of side effects between the trazodone and placebo groups. However, comparisons between trazodone and imipramine indicated the incidence of side effects was significantly lower in the trazodone group.

  16. Anticholinergic-responsive gait freezing in a patient with pantothenate kinase-associated neurodegeneration.

    PubMed

    Lyoo, Chul Hyoung; Prokisch, Holger; Meitinger, Thomas; Lee, Seung Yeob; Kim, Do Hyoun; Lee, Myung Sik

    2008-01-30

    A 43-year-old male patient suddenly developed freezing of gait (FOG) when making a first step, turning, or passing through a narrow path. Dystonic plantar flexion of his left foot always accompanied with FOG. He could walk without FOG when stepping on visual cues. Brain magnetic resonance imaging study showed typical "eye of the tiger" sign in the globus pallidus. He had heterozygous mutations in the exons 3 and 4 in the PANK2 gene. His FOG dramatically responded to the anticholinergic treatment. We report the first instance of a patient with genetically confirmed pantothenate kinase associated neurodegeneration showing typical FOG that responded to anticholinergic treatment. 2007 Movement Disorder Society

  17. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of "Anticholinergic Spectrum Disorders".

    PubMed

    Hori, Koji; Konishi, Kimiko; Hosoi, Misa; Tomioka, Hiroi; Tani, Masayuki; Kitajima, Yuka; Hachisu, Mitsugu

    2016-01-01

    Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of "anticholinergic spectrum disorders," which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh.

  18. Pirenzepine versus scopolamine methyl bromide in double-contrast barium enema study of large bowel.

    PubMed

    Marraccini, P; Braccini, G; Marrucci, A; Boraschi, P; Bertellotti, L; Testa, R

    1996-01-01

    To evaluate the usefulness of pirenzepine for diagnostic double-contrast barium enema study of the large bowel, pirenzepine and scopolamine methyl bromide (SMB) were compared in a single, blind, randomized trial. Sixty consecutive patients were enrolled in the study. Quantitative analysis of bowel distention was done by measuring the maximum diameter of the transverse colon before and after drug administration. Four independent observers blindly evaluated distention and mucosal coating of the large bowel and global quality of the images. No differences were found in the diagnostic performance between the two drugs. However, pirenzepine induced a slight but significantly larger distention of the large bowel (68 +/- 12 vs. 65 +/- 8 mm, p = 0.02). Heart rate and rhythm during the study were recorded by ECG. SMB induced tachycardia in all patients (from 72 +/- 15 to 98 +/- 24 beats/min, p < 0.01), whereas pirenzepine did not (from 76 +/- 13 to 78 +/- 20, p = NS). After SMB, one-patient exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Pirenzepine had a diagnostic performance similar to SMB in avoiding adverse effects elicited by SMB.

  19. Treatment of severe motion sickness with antimotion sickness drug injections

    NASA Technical Reports Server (NTRS)

    Graybiel, Ashton; Lackner, James R.

    1987-01-01

    This report concerns the use of intramuscular injections of scopolamine, promethazine, and dramamine to treat severely motion sick individuals participating in parabolic flight experiments. The findings indicate that a majority of individuals received benefit from 50-mg injections of promethazine or 0.5 mg-injections of scopolamine. By contrast, 50-mg injections of dramamine and 25-mg injections of promethazine were nonbeneficial. The use of antimotion drug injections for treating space motion sickness is discussed.

  20. Treatment of severe motion sickness with antimotion sickness drug injections

    NASA Technical Reports Server (NTRS)

    Graybiel, Ashton; Lackner, James R.

    1987-01-01

    This report concerns the use of intramuscular injections of scopolamine, promethazine, and dramamine to treat severely motion sick individuals participating in parabolic flight experiments. The findings indicate that a majority of individuals received benefit from 50-mg injections of promethazine or 0.5 mg-injections of scopolamine. By contrast, 50-mg injections of dramamine and 25-mg injections of promethazine were nonbeneficial. The use of antimotion drug injections for treating space motion sickness is discussed.

  1. Ethological analysis of scopolamine treatment or pretreatment in morphine dependent rats.

    PubMed

    Xiang, Xiao-Hui; Wang, Hui-Ling; Wu, Wei-Ran; Guo, Yuan; Cao, Dong-Yuan; Wang, Hui-Sheng; Zhao, Yan

    2006-06-15

    Although scopolamine is currently used to treat morphine addiction in humans, its extensive actions on behaviors have not been systematically analyzed yet, and the underlying mechanisms of its effects still remain ambiguous. The present study was carried out to clarify the possible mechanisms by evaluating the effects of scopolamine pretreatment and treatment on naloxone-precipitated withdrawal signs and some of other general behaviors in morphine dependent rats. Our results showed that scopolamine pretreatment and treatment attenuated naloxone-precipitated withdrawal signs including jumping, writhing posture, weight loss, genital grooming, teeth-chattering, ptosis, diarrhea and irritability, except for wet dog shakes, while general behaviors such as water intake, urine volume and morphine excretion in urine were increased. Our findings suggest that scopolamine has significant actions in the treatment of opiate addiction, which might result from increasing morphine excretion from urine.

  2. Estrogen levels modify scopolamine-induced amnesia in gonadally intact rats.

    PubMed

    de Macêdo Medeiros, André; Izídio, Geison Souza; Sousa, Diego Silveira; Macedo, Priscila Tavares; Silva, Anatildes Feitosa; Shiramizu, Victor Kenji Medeiros; Cabral, Alicia; Ribeiro, Alessandra Mussi; Silva, Regina Helena

    2014-08-04

    Previous studies suggested that estrogen plays a role in cognitive function by modulating the cholinergic transmission. However, most of the studies dealing with this subject have been conducted using ovariectomized rats. In the present study we evaluated the effects of physiological and supra-physiological variation of estrogen levels on scopolamine-induced amnesia in gonadally intact female rats. We used the plus-maze discriminative avoidance task (PMDAT) in order to evaluate anxiety levels and motor activity concomitantly to the memory performance. In experiment 1, female Wistar rats in each estrous cycle phase received scopolamine (1 mg/kg) or saline i.p. 20 min before the training session in the PMDAT. In experiment 2, rats in diestrus received estradiol valerate (1 mg/kg) or sesame oil i.m., and scopolamine (1 mg/kg) or saline i.p., 45 min and 20 min before the training, respectively. In experiment 3, rats in diestrus received scopolamine (1 mg/kg) or saline i.p. 20 min before the training, and estradiol valerate (1 mg/kg) or sesame oil i.m. immediately after the training session. In all experiments, a test session was performed 24 h later. The main results showed that: (1) scopolamine impaired retrieval and induced anxiolytic and hyperlocomotor effects in all experiments; (2) this cholinergic antagonist impaired acquisition only in animals in diestrus; (3) acute administration of estradiol valerate prevented the learning impairment induced by scopolamine and (4) interfered with memory consolidation process. The results suggest that endogenous variations in estrogen levels across the estrous cycle modulate some aspects of memory mediated by the cholinergic system. Indeed, specifically in diestrus, a stage with low estrogen levels, the impairment produced by scopolamine on the acquisition was counteracted by exogenous administration of the hormone, whereas the posttraining treatment potentiated the negative effects of scopolamine during the consolidation phase

  3. A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel

    DTIC Science & Technology

    2008-08-18

    were recruited and randomized to one of three treatment groups [intranasal scopolamine gel (IN SCOP ); oral scopolamine (PO SCOP ); or placebo] and...head movements tolerated among groups and pharmacotherapeutics for IN SCOP and PO SCOP were determined by salivary assay. Side-effect profiles for all...cognitive battery, VA, or KSS, p > 0.05. An ANOVA revealed a significant decrease in heart rate over time for IN SCOP and PO SCOP versus placebo at

  4. Extinction and recovery of an avoidance memory impaired by scopolamine.

    PubMed

    Navarro, N M; Krawczyk, M C; Boccia, M M; Blake, M G

    2017-03-15

    Pre-training administration of scopolamine (SCP) resembles situations of cholinergic dysfunction, leading to memory impairment of mice trained in an inhibitory avoidance task. We suggest here that SCP does not impair memory formation, but acquisition is affected in a way that reduces the strength of the stored memory, thus making this memory less able to control behavior when tested. Hence, a memory trace is stored, but is poorly expressed during the test. Although weakly expressed, this memory shows extinction during successive tests, and can be strengthened by using a reminder. Our results indicate that memories stored under cholinergic dysfunction conditions seem absent or lost, but are in fact present and experience common memory processes, such as extinction, and could be even recovered by using appropriate protocols.

  5. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer’s disease

    PubMed Central

    Bajo, R.; Pusil, S.; López, M. E.; Canuet, L.; Pereda, E.; Osipova, D.; Maestú, F.; Pekkonen, E.

    2015-01-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer’s disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD. PMID:26130273

  6. Effects of vitexin on scopolamine-induced memory impairment in rats.

    PubMed

    Abbasi, Esmail; Nassiri-Asl, Marjan; Sheikhi, Mehdi; Shafiee, Mahsa

    2013-06-30

    Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The present study aimed to investigate the effects of vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in such plants as tartary buckwheat sprouts, wheat leaves phenolome, Mimosa pudica Linn and Passiflora spp, on scopolamine-induced memory impairment in rats. To achieve this goal, we assessed the effects of vitexin on memory retrieval in the presence or absence of scopolamine using a step-through passive avoidance trial. In the first part of the study, vitexin (25, 50, and 100 microM) was administered intracerebroventricularly (i.c.v.) before acquisition trials. In the second part, vitexin, at the same doses, was administered before scopolamine (10 microg, i.c.v.) and before the acquisition trials. During retention tests, vitexin (100 microM) in the absence of scopolamine significantly increased the step-through latencies compared to scopolamine. In addition, vitexin (100 microM) significantly reversed the shorter step-through latencies induced by scopolamine (P < 0.05). These results indicate that vitexin has a potential role in enhancing memory retrieval. A possible mechanism is modulation of cholinergic receptors; however, other mechanisms may be involved in its effects in acute exposure.

  7. Ascorbic acid attenuates scopolamine-induced spatial learning deficits in the water maze.

    PubMed

    Harrison, F E; Hosseini, A H; Dawes, S M; Weaver, S; May, J M

    2009-12-28

    Vitamin C (ascorbate) has important antioxidant functions that can help protect against oxidative stress in the brain and damage associated with neurodegenerative disorders such as Alzheimer's disease. When administered parenterally ascorbate can bypass saturable uptake mechanisms in the gut and thus higher tissue concentrations can be achieved than by oral administration. In the present study we show that ascorbate (125 mg/kg) administered intraperitoneally (i.p.) 1-h before testing, partially attenuated scopolamine-induced (1 mg/kg i.p.) cognitive deficits in Morris water maze performance in young mice. Cumulative search error, but not escape latency nor path length, was significantly improved during acquisition in ascorbate plus scopolamine-treated mice although performance did not equal that of control mice. During the probe trial, scopolamine led to increased search error and chance level of time spent in the platform quadrant, whereas mice pre-treated with ascorbate prior to scopolamine did not differ from control mice on these measures. Ascorbate had no effect on unimpaired, control mice and neither did it reduce the peripheral, activity-increasing effects of scopolamine. Ascorbate alone increased acetylcholinesterase activity in the medial forebrain area but had no effect in cortex or striatum. This change, and its action against the amnestic effects of the muscarinic antagonist scopolamine, suggest that ascorbate may be acting in part via altered cholinergic signaling. However, further investigation is necessary to isolate the cognition-enhancing effects of ascorbate.

  8. Neuroprotective effects of Citrus reticulata in scopolamine-induced dementia oxidative stress in rats.

    PubMed

    El-Khadragy, Manal F; Al-Olayan, Ebtesam M; Abdel Moneim, Ahmed E

    2014-01-01

    The purpose of the study was to evaluate the potential effects of Citrus reticulate (mandarin) peel methanolic extract (MPME) on memory dysfunction in rats. Memory impairment was produced by scopolamine (1.4 mg/kg, intraperitoneally injected). Brain acetylcholinesterase enzyme (AChE) activity was measured to assess the central cholinergic activity. This study also investigated the effect of scopolamine on norepinephrine, dopamine and serotonin content in rat hippocampus, striatum and cerebral cortex. In addition, the levels of brain lipid peroxidation (LPO), nitric oxide (NO) and glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced a significant impairment of central cholinergic activity in rats, as indicated by a marked increase in AChE activity. The impairment of the cholinergic system was associated with a significant alternation in brain monoamines. Scopolamine administration also caused oxidant damage (elevation in LPO and NO and reduction in GSH levels). Pretreatment of MPME (250 mg/kg, orally administered) significantly reduced scopolamine-induced alternation in brain monoamines with an attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress. It is concluded that administration of mandarin peel extract, demonstrating antioxidant activity, may be of value for dementia exhibiting elevated brain oxidative status.

  9. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease.

    PubMed

    Bajo, R; Pusil, S; López, M E; Canuet, L; Pereda, E; Osipova, D; Maestú, F; Pekkonen, E

    2015-07-01

    Scopolamine administration may be considered as a psychopharmacological model of Alzheimer's disease (AD). Here, we studied a group of healthy elderly under scopolamine to test whether it elicits similar changes in brain connectivity as those observed in AD, thereby verifying a possible model of AD impairment. We did it by testing healthy elderly subjects in two experimental conditions: glycopyrrolate (placebo) and scopolamine administration. We then analyzed magnetoencephalographic (MEG) data corresponding to both conditions in resting-state with eyes closed. This analysis was performed in source space by combining a nonlinear frequency band-specific measure of functional connectivity (phase locking value, PLV) with network analysis methods. Under scopolamine, functional connectivity between several brain areas was significantly reduced as compared to placebo, in most frequency bands analyzed. Besides, regarding the two complex network indices studied (clustering and shortest path length), clustering significantly decreased in the alpha band while shortest path length significantly increased also in alpha band both after scopolamine administration. Overall our findings indicate that both PLV and graph analysis are suitable tools to measure brain connectivity changes induced by scopolamine, which causes alterations in brain connectivity apparently similar to those reported in AD.

  10. Anthriscus nemorosa essential oil inhalation prevents memory impairment, anxiety and depression in scopolamine-treated rats.

    PubMed

    Bagci, Eyup; Aydin, Emel; Ungureanu, Eugen; Hritcu, Lucian

    2016-12-01

    Anthriscus nemorosa (Bieb.) Sprengel is used for medicinal purposes in traditional medicine around the world, including Turkey. Ethnobotanical studies suggest that Anthriscus essential oil could improve memory in Alzheimer's disease. The current study was hypothesized to investigate the beneficial effects of inhaled Anthriscus nemorosa essential oil on memory, anxiety and depression in scopolamine-treated rats. Anthriscus nemorosa essential oil was administered by inhalation in the doses of 1% and 3% for 21 continuous days and scopolamine (0.7mg/kg) was injected intraperitoneally 30min before the behavioral testing. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by elevated plus-maze and forced swimming tests. As expected, the scopolamine alone-treated rats exhibited the following: decrease the percentage of the spontaneous alternation in Y-maze test, increase the number of working and reference memory errors in radial arm-maze test, decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. However, dual scopolamine and Anthriscus nemorosa essential oil-treated rats showed significant improvement of memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. These results suggest that Anthriscus nemorosa essential oil inhalation can prevent scopolamine-induced memory impairment, anxiety and depression.

  11. Scopolamine rapidly increases mTORC1 signaling, synaptogenesis, and antidepressant behavioral responses

    PubMed Central

    Voleti, Bhavya; Navarria, Andrea; Liu, Rong-Jian; Banasr, Mounira; Li, Nanxin; Terwilliger, Rose; Sanacora, Gerard; Eid, Tore; Aghajanian, George; Duman, Ronald S.

    2013-01-01

    Background Clinical studies report that scopolamine, an acetylcholine muscarinic receptor antagonist, produces rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic response have not been determined. The present study examines the role of the mammalian target of rapamycin complex 1 (mTORC1) and synaptogenesis, which have been implicated in the rapid actions of NMDA receptor antagonists. Methods The influence of scopolamine on mTORC1 signaling was determined by analysis of the phosphorylated and activated forms of mTORC1 signaling proteins in the prefrontal cortex (PFC). The numbers and function of spine synapses were analyzed by whole cell patch clamp recording and 2-photon image analysis of PFC neurons. The actions of scopolamine were examined in the forced swim test in the absence or presence of selective mTORC1 and AMPA receptor inhibitors. Results The results demonstrate that a single, low dose of scopolamine rapidly increases mTORC1 signaling and the number and function of spine synapses in layer V pyramidal neurons in the PFC. Scopolamine administration also produces an antidepressant response in the forced swim test that is blocked by pretreatment with the mTORC1 inhibitor or by a glutamate AMPA receptor antagonist. Conclusions Taken together, the results demonstrate that the antidepressant actions of scopolamine require mTORC1 signaling and are associated with increased glutamate transmission, and synaptogenesis, similar to NMDA receptor antagonists. These findings provide novel targets for safer and more efficacious rapid acting antidepressant agents. PMID:23751205

  12. Anticholinergic Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study

    PubMed Central

    Marcum, Zachary A.; Perera, Subashan; Thorpe, Joshua M.; Switzer, Galen E.; Gray, Shelly L.; Castle, Nicholas G.; Strotmeyer, Elsa S.; Simonsick, Eleanor M.; Bauer, Douglas C.; Shorr, Ronald I.; Studenski, Stephanie A.; Hanlon, Joseph T.

    2015-01-01

    Background Although it is generally accepted that anticholinergic use may lead to a fall, results from studies assessing the association between anticholinergic use and falls are mixed. In addition, direct evidence of an association between use of anticholinergic medications and recurrent falls among community-dwelling elders is not available. Objective To assess the association between anticholinergic use across multiple anticholinergic subclasses, including over-the-counter medications, and recurrent falls. Methods This was a longitudinal analysis of 2948 participants, with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997–2004). Self-reported use of anticholinergic medication was identified at years 1, 2, 3, 5, and 6 as defined by the list from the 2015 American Geriatrics Society Beers Criteria. Dosage and duration were also examined. The main outcome was recurrent falls (≥2) in an ensuing 12-month period from each medication data collection. Results Using multivariable generalized estimating equation models, controlling for demographic, health status/behaviors, and access-to-care factors, a 34% increase in likelihood of recurrent falls in anticholinergic users (adjusted odds ratio = 1.34; 95% CI = 0.93–1.93) was observed, but the results were not statistically significant; similar results were found with higher doses and longer duration of use. Conclusion Increased point estimates suggest an association of anticholinergic use with recurrent falls, but the associations did not reach statistical significance. Future studies are needed for more definitive evidence and to examine other measures of anticholinergic burden and associations with more intermediate adverse effects such as cognitive function. PMID:26228936

  13. Anticholinergic versus beta 2-agonist on gas exchange in COPD: a comparative study in 15 patients.

    PubMed

    Pillet, O; Manier, G; Castaing, Y

    1998-02-01

    beta-agonist bronchodilators are known to influence gas exchange and ventilation-perfusion relationships in asthmatic patients, where they induce hypoxaemia via hypoxic vasoconstriction. As this effect could have serious consequences in chronic obstructive pulmonary disease (COPD) patients with chronic hypoxaemia, alternative agents have been sought. It has been shown that inhaled anticholinergic drugs may be of value in this condition. In the present study, we compared the effects of salbutamol (Sb) and ipratropium bromide (IB) inhalation on gas exchange in 15 patients with stable COPD. All patients had a history of COPD (mean arterial oxygen tension (Pa,O2) = 8.2 +/- 1.0 kPa (61.8 +/- 7.3 mmHg) forced expiratory volume in one second (FEV1) = 39 +/- 12%; FEV1/vital capacity (VC) = 42 +/- 6%) and no evidence of acute respiratory failure. Haemodynamic and gas exchange data were recorded after right catheterization by the multiple inert gas elimination technique. Measurements were made under basal conditions, after two puffs of freon propellant (placebo) and after two puffs of either 200 micrograms Sb or 200 micrograms IB in a randomized design. Sb and IB reduced airway resistances to the same extent, but had no significant influence on the haemodynamic and ventilation parameters. There was a slight but significant decrease in arterial carbon dioxide tension (Pa,CO2) = 6.0 +/- 0.8 versus 6.4 +/- 0.8 kPa (45.4 +/- 5.9 versus 47.9 +/- 6.3 mmHg) p < 0.05 with an enhanced perfusion distribution heterogeneity and a slight improvement in ventilation homogeneity shown by a decrease of the decimal logarithm of SD of the ventilation distribution (LogSDV) after inhalation of IB relative to control. Since these alterations did not affect arterial oxygen tension we concluded that inhalation of these doses of salbutamol or ipratropium bromide do not affect gas exchange in patients with stable chronic obstructive pulmonary disease. The normal home treatment: inhalation of two

  14. Limitations of anticholinergic cycling in patients with overactive bladder (OAB) with urinary incontinence (UI): results from the CONsequences of Treatment Refractory Overactive bLadder (CONTROL) study.

    PubMed

    Chancellor, Michael B; Yehoshua, Alon; Waweru, Catherine; Globe, Denise; Cheng, I-Ning; Campbell, Karen L; Joshi, Manher; Pulicharam, Riya

    2016-07-01

    To describe treatment patterns and outcomes in wet-overactive bladder (OAB) patients treated with anticholinergics. This study was a retrospective claims analysis linked to a one-time patient survey of members of a regional medical group located in California. Participants met the following criteria: received anticholinergic therapy between January 2008 and May 2012, based on pharmacy claims; had a diagnosis of OAB; and reported having ≥1 urinary incontinence (UI) episode per day at the time of the survey. Outcomes included the number of anticholinergics cycled through from treatment initiation until the end of follow-up (May 31, 2013); frequency of UI episodes; and patient requests for additional help for their OAB symptoms. A total of 620 patients were enrolled into the study. During the follow-up period, patients cycled through 1 to 6 unique anticholinergics; 65 % of the study population used only 1 anticholinergic, while 35 % used ≥2 anticholinergics. Patients reported experiencing an average of 3.5 UI episodes per day (3.6, 3.3, and 3.4 episodes for 1, 2, and ≥3 anticholinergics used, respectively), and over 80 % of patients requested additional help for their OAB symptoms, irrespective of how many anticholinergics were attempted. UI symptom burden and adherence to therapy did not change as patients attempted more anticholinergic therapies. These results suggest that for patients who remain incontinent after attempting an anticholinergic, cycling on additional anticholinergics may not provide any additional benefit, resulting in sub-optimal care.

  15. Amelioration of scopolamine induced cognitive dysfunction and oxidative stress by Inonotus obliquus - a medicinal mushroom.

    PubMed

    Giridharan, Vijayasree Vayalanellore; Thandavarayan, Rajarajan Amirthalingam; Konishi, Tetsuya

    2011-06-01

    The present study was aimed to investigate the cognitive enhancing and anti-oxidant activities of Inonotus obliquus (Chaga) against scopolamine-induced experimental amnesia. Methanolic extract of Chaga (MEC) at 50 and 100 mg kg (-1)doses were administered orally for 7 days to amnesic mice. Learning and memory was assessed by passive avoidance task (PAT) and Morris water maze (MWM) test. Tacrine (THA, 10 mg kg (-1), orally (p.o)) used as a reference drug. To elucidate the mechanism of the cognitive enhancing activity of MEC, the activities of acetylcholinesterase (AChE), anti-oxidant enzymes, the levels of acetylcholine (ACh) and nitrite of mice brain homogenates were evaluated. MEC treatment for 7 days significantly improved the learning and memory as measured by PAT and MWM paradigms. Further, MEC significantly reduced the oxidative-nitritive stress, as evidenced by a decrease in malondialdehyde and nitrite levels and restored the glutathione and superoxide dismutase levels in a dose dependent manner. In addition, MEC treatment significantly decreased the AChE activity in both the salt and detergent-soluble fraction of brain homogenates. Further, treatment with MEC restored the levels of ACh as did THA. Thus, the significant cognitive enhancement observed in mice after MEC administration is closely related to higher brain anti-oxidant properties and inhibition of AChE activity. These findings stress the critical impact of Chaga, a medicinal mushroom, on the higher brain functions like learning and memory.

  16. Myricetin ameliorates scopolamine-induced memory impairment in mice via inhibiting acetylcholinesterase and down-regulating brain iron.

    PubMed

    Wang, Beiyun; Zhong, Yuan; Gao, Chengjie; Li, Jingbo

    2017-08-19

    The aim of our study was to investigate to investigate the effect of myricetin on Alzheimer's disease (AD) and its underlying mechanisms. In our study, Myricetin effectively attenuated Fe(2+)-induced cell death in SH-SY5Y cells in vitro. In a mouse model of AD, myricetin treatment significantly reversed scopolamine-induced cognitive deficits deriving from a novel action of inhibiting acetylcholinesterase (AChE) and down-regulating brain iron. Furthermore, Myricetin treatment reduced oxidative damage and increased antioxidant enzymes activity in mice. Interestingly, the effect of myricetin was largely abolished by high iron diet. Therefore we suggested that treatment with myricetin attenuated cognitive deficits in mice via inhibiting AChE and brain iron regulation. In addition, myricetin reduce iron contents may via inhibiting transferrin receptor 1 (TrR1) expression. In conclusion, accumulated data demonstrates that myricetin is a potential multifunctional drug for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review.

    PubMed

    Drevets, Wayne C; Zarate, Carlos A; Furey, Maura L

    2013-06-15

    The muscarinic cholinergic receptor system has been implicated in the pathophysiology of depression, with physiological evidence indicating this system is overactive or hyperresponsive in depression and with genetic evidence showing that variation in genes coding for receptors within this system are associated with higher risk for depression. In studies aimed at assessing whether a reduction in muscarinic cholinergic receptor function would improve depressive symptoms, the muscarinic receptor antagonist scopolamine manifested antidepressant effects that were robust and rapid relative to conventional pharmacotherapies. Here, we review the data from a series of randomized, double-blind, placebo-controlled studies involving subjects with unipolar or bipolar depression treated with parenteral doses of scopolamine. The onset and duration of the antidepressant response are considered in light of scopolamine's pharmacokinetic properties and an emerging literature that characterizes scopolamine's effects on neurobiological systems beyond the cholinergic system that appear relevant to the neurobiology of mood disorders. Scopolamine infused at 4.0 μg/kg intravenously produced robust antidepressant effects versus placebo, which were evident within 3 days after the initial infusion. Placebo-adjusted remission rates were 56% and 45% for the initial and subsequent replication studies, respectively. While effective in male and female subjects, the change in depression ratings was greater in female subjects. Clinical improvement persisted more than 2 weeks following the final infusion. The timing and persistence of the antidepressant response to scopolamine suggest a mechanism beyond that of direct muscarinic cholinergic antagonism. These temporal relationships suggest that scopolamine-induced changes in gene expression and synaptic plasticity may confer the therapeutic mechanism.

  18. Deer bone extract prevents against scopolamine-induced memory impairment in mice.

    PubMed

    Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun; Kim, Mee Ree

    2015-02-01

    Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1-42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.

  19. Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats.

    PubMed

    Hasanein, Parisa; Mahtaj, Azam Kazemian

    2015-01-12

    Rosmarinic acid (RA) is a natural phenol that exerts different biological activities, such as antioxidant activity and neuroprotective effects. In this study, we hypothesized that administration of RA (8, 16, and 32 mg/kg, p.o.) for 7 days would effect on scopolamine-induced cognitive dysfunction as an extensively used model of cognitive impairment. The rats were divided into 10 groups. The acquisition trial was done 1h after the last administration of RA. Animals were divided into control, RA (8, 16, and 32 mg/kg) and donepezil (2 mg/kg) treated controls, scopolamine, RA (8, 16, and 32 mg/kg), and donepezil (2 mg/kg) treated scopolamine groups. Memory impairment was induced by scopolamine treatment (1 mg/kg, i.p.) 30 min after the administration of RA, donepezil, or saline. Scopolamine administration caused cognition deficits in the PAL and memory paradigm. While orally RA administration (16 and 32 mg/kg) improved learning and memory in control rats, it reversed learning and memory deficits of scopolamine received groups. Administration of RA at the dose of 8 mg/kg did not alter cognitive function in control and scopolamine treated groups. The combination of anticholinesterase, neuroprotective, and antioxidant properties of RA may all be responsible for the observed effects. These results indicate the beneficial effects of subchronic RA administration in passive avoidance learning and memory in control rats as well as in a pharmacological model of cholinergic deficit which continue to expand the knowledge base in creating new treatment strategies for cognition deficits and dementia. Of course, further studies are warranted for clinical use of RA in the management of demented subjects.

  20. Deer Bone Extract Prevents Against Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun

    2015-01-01

    Abstract Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1–42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine. PMID:25546299

  1. Over-Prescribed Medications, Under-Appreciated Risks: A Review of the Cognitive Effects of Anticholinergic Medications in Older Adults.

    PubMed

    Britt, Daniel M I; Day, Gregory S

    2016-01-01

    Anticholinergic medications are associated with adverse cognitive effects in cognitively normal and impaired individuals, with a greater magnitude of effect observed in individuals with preexisting cognitive impairment due to Alzheimer disease.

  2. Health Resource Utilization and Cost for Patients with Incontinent Overactive Bladder Treated with Anticholinergics.

    PubMed

    Yehoshua, Alon; Chancellor, Michael; Vasavada, Sandip; Malone, Daniel C; Armstrong, Edward P; Joshi, Manher; Campbell, Karen; Pulicharam, Riya

    2016-04-01

    Overactive bladder (OAB) is a common medical condition with significant economic and humanistic burden. Inadequately managed OAB may exacerbate or result in comorbidities such as depression, falls, and urinary tract infections, which can further increase the burden to the health care system. Anticholinergics are often prescribed for management of OAB with urinary incontinence ("wet" OAB). However, research has shown that patient adherence and persistence to anticholinergic therapy is poor, with approximately 80% of patients ultimately failing their first prescribed anticholinergic medication within the first year. While there has been a fair amount of research on the economic burden of OAB, the real-world impact of initiating anticholinergic therapy in patients with wet OAB has not been well studied. To compare falls/fractures, anxiety/depression, health care resource utilization, and health care costs between a cohort of patients with wet OAB who initiated anticholinergic therapy and a matched cohort of patients without OAB. This study was a retrospective medical and pharmacy claims analysis. Cases were members of a primary care-based, multispecialty physician medical group located in California. Cases were eligible for inclusion if they were prescribed anticholinergic therapy between January 2008 and May 2012 based on pharmacy claims, had a diagnosis of OAB, and reported having ≥ 1 urinary incontinence episode per day. Wet OAB cases were matched to non-OAB controls in a 1:3 ratio based on sex, age, and observation time. Medical and pharmacy claims data were used to analyze patient comorbidities, as well as track health care resource utilization (HRU) and direct payer costs. After initiating anticholinergic therapy, wet OAB patients had a 46% higher adjusted risk of experiencing falls/fractures (P < 0.001) and a 33% higher adjusted risk of experiencing depression/anxiety (P = 0.022) than non-OAB patients. Wet OAB was significantly associated with increased HRU

  3. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders”

    PubMed Central

    Tomioka, Hiroi; Hachisu, Mitsugu

    2016-01-01

    Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of “anticholinergic spectrum disorders,” which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh. PMID:27738546

  4. Heat Tolerance and the Peripheral Effects of Anticholinergics

    DTIC Science & Technology

    1988-01-30

    from in vitro dose - response assays on isolated tissues suspended in organ baths, where the concentration of drugs can be carefully controlled. It would...obtaining accurate and reproducible dose - response data non-invasively from the eccrine sweat gland system, (2) to compare effectiveness of different locally...applied cholinergic muscarinic antagonists in altering dose - response patterns of eccrine glands to locally applied cholinergic agonists, (3) to study

  5. Dual Use of Bladder Anticholinergics and Cholinesterase Inhibitors: Long-Term Functional and Cognitive Outcomes

    PubMed Central

    Sink, Kaycee M.; Thomas, Joseph; Xu, Huiping; Craig, Bruce; Kritchevsky, Steven; Sands, Laura P.

    2015-01-01

    OBJECTIVES To determine the cognitive and functional consequences of dual use of cholinesterase inhibitors (ChIs) and the bladder anticholinergics oxybutynin or tolterodine. DESIGN Prospective cohort study. SETTING Nursing homes (NHs) in the state of Indiana. PARTICIPANTS Three thousand five hundred thirty-six Medicaid-eligible NH residents aged 65 and older taking a ChI between January 1, 2003, and December 31, 2004. Residents were excluded if they were taking an anticholinergic other than oxybutynin or tolterodine. MEASUREMENTS Indiana Medicaid claims data were merged with data from the Minimum Data Set (MDS). Repeated-measures analyses were performed to assess the effects of dual therapy on change in cognitive function measured using the MDS Cognition Scale (MDS-COGS; scored 0–10) and change in activity of daily living (ADL) function using the seven ADL items in the MDS (scored 0–28). Potential covariates included age, sex, race, number of medications, and Charlson Comorbidity Index score. RESULTS Three hundred seventy-six (10.6%) residents were prescribed oxybutynin or tolterodine concomitantly with a ChI. In residents in the top quartile of ADL function, ADL function declined an average of 1.08 points per quarter when not taking bladder anticholinergics (ChI alone), compared with 1.62 points per quarter when taking dual therapy, a 50% greater rate in quarterly decline in ADL function (P =.01). There was no excess decline attributable to dual therapy in MDS-COGS scores or in ADL function for residents who started out with lower functioning. CONCLUSION In higher-functioning NH residents, dual use of ChIs and bladder anticholinergics may result in greater rates of functional decline than use of ChIs alone. The MDS-COGS may not be sensitive enough to detect differences in cognition due to dual use. PMID:18384584

  6. Differential effects of 3,4-methylenedioxymethamphetamine, methamphetamine, meta-Chlorophenylpiperazine, and scopolamine on behavioral repetition versus variation in rats.

    PubMed

    Olsen, Rebecca A; Macaskill, Anne C; Harper, David N

    Acute administration of drugs of abuse, such as MDMA and methamphetamine, disrupts performance on many operant tasks, for example, those used to study memory. This might occur in part because drugs make behavior, in general, more repetitive or more variable, or because they produce a more global disruption to performance. The current study explored this across two experiments by employing Neuringer's 'reinforced variability' procedure. Varied behavior was reinforced at some times during the session and repetitive behavior at other times; lights signalled the behavior required. This procedure allowed an investigation of whether a particular drug made behavior more variable (affected behavior when repetition was required), more repetitive (affected behavior when variability was required), or produced a global disruption (affected both components). In Experiment 1, MDMA increased variability while methamphetamine affected both components. In Experiment 2, m-CPP affected both components while scopolamine affected both components at lower doses and increased variability at higher doses. These results indicate both that the reinforced variability procedure can be used to isolate the specific effects of drugs of abuse on the variability of behavior, and that the specific impact of a given drug needs to be considered when interpreting pharmacological disruptions to operant task performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Determination of Scopolamine in Human Saliva Using Solid Phase Extraction and LC/MS/MS

    NASA Technical Reports Server (NTRS)

    Wang, Zuwei; Vaksman, Zalman; Boyd, Jason; Putcha, Lakshmi

    2007-01-01

    Purpose: Scopolamine is the preferred treatment for motion sickness during space flight because of its quick onset of action, short half-life and favorable side-effect profile. The dose administered depends on the mode of administration and usually ranges between 0.1 and 0.8 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids by using conventional HPLC methods. To measure scopolamine in saliva and thereby to evaluate the pharmacokinetics of scopolamine, we developed an LC/MS/MS method using off-line solid phase extraction. Method: Samples (0.5mL) were loaded onto Waters Oasis HLB co-polymer cartridges (10 mg, 1 mL) and eluted with 0.5 mL methanol without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 4 minutes. The mobile phase for separation was 90:10 (v/v) methanol: ammonium acetate (2 mM) in water, pH 5.0 +/- 0.1. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 yields 138.1 and internal standard (IS) hyoscyamine m/z = 290.2 yields 124.1. Results: The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at 1.7 and 3.2 min respectively. The linear range is 50-5000 pg/mL for scopolamine in saliva with correlation coefficients > 0.99 with a CV < 0.5 %. The intra-day and inter-day CVs are < 15 % for quality control samples with concentrations of 75, 300, 750 and 3000 pg/mL of scopolamine in human saliva. Conclusion: Solid phase extraction allows more rapid sample preparation and greater precision than liquid extraction. Furthermore, we increased the sensitivity and specificity by adjusting the LC mobile phase and using an MS

  8. Determination of Scopolamine in Human Saliva Using Solid Phase Extraction and LC/MS/MS

    NASA Technical Reports Server (NTRS)

    Wang, Zuwei; Vaksman, Zalman; Boyd, Jason; Putcha, Lakshmi

    2007-01-01

    Purpose: Scopolamine is the preferred treatment for motion sickness during space flight because of its quick onset of action, short half-life and favorable side-effect profile. The dose administered depends on the mode of administration and usually ranges between 0.1 and 0.8 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids by using conventional HPLC methods. To measure scopolamine in saliva and thereby to evaluate the pharmacokinetics of scopolamine, we developed an LC/MS/MS method using off-line solid phase extraction. Method: Samples (0.5mL) were loaded onto Waters Oasis HLB co-polymer cartridges (10 mg, 1 mL) and eluted with 0.5 mL methanol without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 4 minutes. The mobile phase for separation was 90:10 (v/v) methanol: ammonium acetate (2 mM) in water, pH 5.0 +/- 0.1. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 yields 138.1 and internal standard (IS) hyoscyamine m/z = 290.2 yields 124.1. Results: The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at 1.7 and 3.2 min respectively. The linear range is 50-5000 pg/mL for scopolamine in saliva with correlation coefficients > 0.99 with a CV < 0.5 %. The intra-day and inter-day CVs are < 15 % for quality control samples with concentrations of 75, 300, 750 and 3000 pg/mL of scopolamine in human saliva. Conclusion: Solid phase extraction allows more rapid sample preparation and greater precision than liquid extraction. Furthermore, we increased the sensitivity and specificity by adjusting the LC mobile phase and using an MS

  9. Comparative neurotransmitter reuptake and anticholinergic potencies of the 8-hydroxy metabolites of clomipramine.

    PubMed

    Núñez, R; Perel, J M

    1995-01-01

    We hypothesize that 8-hydroxy-clomipramine (8-OH-CMI), the major hydroxy metabolite of clomipramine (CMI), may have antidepressant properties with less anticholinergic potency than CMI. We compared the potencies of 8-OH-CMI and CMI for inhibition of serotonin and norepinephrine reuptake and the potencies of these compounds for blockade of muscarinic receptors. We also compared the antimuscarinic potencies of desmethylclomipramine (DCMI) and 8-hydroxy-desmethylclomipramine (8-OH-DCMI). We found that 8-OH-CMI inhibits the uptake of serotonin and norepinephrine to the same extent as CMI and that 8-OH-CMI has far less antimuscarinic potency than CMI. We also found that 8-OH-DCMI has about one-tenth the antimuscarinic potency of DCMI. Since the therapeutic efficacy of CMI may be related to its effect on the reuptake of neurotransmitters, and since the extent of clinical anticholinergic effects of tricyclic antidepressants has been shown to be related to their in vitro antimuscarinic potencies, these results raise the possibility that 8-OH-CMI may be an analogue of CMI with fewer anticholinergic side effects than the parent compound.

  10. Bitter lupine beans ingestion in a child: a disregarded cause of acute anticholinergic toxicity.

    PubMed

    Daverio, Marco; Cavicchiolo, Maria Elena; Grotto, Paolo; Lonati, Davide; Cananzi, Mara; Da Dalt, Liviana

    2014-12-01

    We describe the case of a 6-year-old girl brought to the emergency department for the sudden onset of anticholinergic syndrome after the ingestion of a few home-made partially debittered lupine beans. She complained of blurry vision, headache, photophobia and nausea. No specific treatment was needed, and the symptoms resolved about 12 h after the exposure. Lupine beans are a popular and worldwide-diffused food. The bitter variety is rich in alkaloids harbouring anticholinergic activity and thus requires a debittering process before lupines can be eaten. Only four cases of acute toxicity, due to the ingestion of incompletely detoxified bitter lupines, have been reported in children so far; notwithstanding the small amount of lupines ingested, three of these cases were lethal. Acute anticholinergic syndrome can arise after the consumption of a wide range of exogenous substances including partially debittered lupine beans. Paediatricians should be aware of bitter lupine toxicity, recognize possible cases of intoxication, ensure a prompt and appropriate supportive treatment and provide appropriate information about their danger.

  11. The Ameliorating Effect of Myrrh on Scopolamine-Induced Memory Impairments in Mice

    PubMed Central

    Baral, Samrat; Cho, Du-Hyong; Pariyar, Ramesh; Yoon, Chi-Su; Chang, Bo-yoon; Kim, Dae-Sung; Cho, Hyoung-Kwon; Kim, Sung Yeon; Oh, Hyuncheol; Kim, Youn-Chul; Kim, Jaehyo; Seo, Jungwon

    2015-01-01

    Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM) on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments. PMID:26635888

  12. Locomotor activating effects of cocaine and scopolamine combinations in rats: isobolographic analysis.

    PubMed

    Thomsen, Morgane

    2014-08-01

    Muscarinic cholinergic receptors are currently receiving renewed interest as viable targets for treating various psychiatric disorders. Dopaminergic and muscarinic systems interact in complex ways. The goal of this study was to quantify the interaction between a systemically administered psychomotor stimulant and muscarinic antagonist at the behavioral level. Through isobolographic analysis of locomotor activity data, we assessed the effects of three cocaine/scopolamine mixtures in terms of deviation from simple dose addition (additivity), at four effect levels. All three mixtures produced some more-than-additive (synergistic) effects, as lower doses were needed to produce the given effects relative to the calculated effect of additive doses. A mixture with comparable contributions from cocaine and scopolamine produced significantly more-than-additive effects at all but the lowest effect level examined. A mostly-cocaine mixture was more-than-additive only at low effect levels, whereas a mostly-scopolamine mixture produced effects more consistent with additivity, with only the highest effect level barely reaching significant synergism. Our study confirms and quantifies previous findings that suggested synergistic effects of stimulants and muscarinic antagonists. The synergism implies that cocaine and scopolamine stimulate locomotor activity through nonidentical pathways, and was most pronounced for a mixture containing cocaine and scopolamine in comparable proportions.

  13. Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation.

    PubMed

    Moosavi, Maryam; Khales, Golnaz Yadollahi; Abbasi, Leila; Zarifkar, Asadollah; Rastegar, Karim

    2012-04-01

    Cholinergic brain activity plays a significant role in memory. Scopolamine a muscarinic cholinergic antagonist is known to induce impairment in Morris water maze performance, the task which is mainly dependent on the hippocampus. It is suggested that hippocampal ERK and Akt activation play roles in synaptic plasticity and some types of learning and memory. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study was aimed to investigate if agmatine could reverse scopolamine-induced memory impairment and possible hippocampal ERK and Akt activity alteration. Adult male Sprague-Dawley rats weighing 200-250 g were randomly assigned into 5 groups. The animals were trained for 3 days in Morris water maze and in day 4 their memory retention was assessed in probe trial which was consisted of a 60 s trial with no platform. Scopolamine (1 mg/kg/ip) or saline were injected 30 min and agmatine (20 or 40 mg/kg/ip) was administered 60 min before each session. The hippocampi were isolated after behavioral studies and western blotting studies on hippocampal lysates were done to determine the levels of activated ERK and Akt. Scopolamine treatment not only impaired water maze learning and memory, but also decreased the amount of phosphorylated (activated) ERK and Akt. Agmatine pre-treatment prevented both the learning impairment and hippocampal ERK and Akt inactivation induced by scopolamine. It seems that agmatine may act as a candidate substance against amnesia.

  14. Brain Network Activation (BNA) reveals scopolamine-induced impairment of visual working memory.

    PubMed

    Reches, Amit; Levy-Cooperman, Naama; Laufer, Ilan; Shani-Hershkovitch, Revital; Ziv, Keren; Kerem, Dani; Gal, Noga; Stern, Yaki; Cukierman, Guy; Romach, Myroslava K; Sellers, Edward M; Geva, Amir B

    2014-09-01

    The overarching goal of this event-related potential (ERP) study was to examine the effects of scopolamine on the dynamics of brain network activation using a novel ERP network analysis method known as Brain Network Activation (BNA). BNA was used for extracting group-common stimulus-activated network patterns elicited to matching probe stimuli in the context of a delayed matching-to-sample task following placebo and scopolamine treatments administered to healthy participants. The BNA extracted networks revealed the existence of two pathophysiological mechanisms following scopolamine, disconnection, and compensation. Specifically, weaker frontal theta and parietal alpha coupling was accompanied with enhanced fronto-centro-parietal theta activation relative to placebo. In addition, using the characteristic BNA network of each treatment as well as corresponding literature-guided selective subnetworks as combined biomarkers managed to differentiate between individual responses to each of the treatments. Behavioral effects associated with scopolamine included delayed response time and impaired response accuracy. These results indicate that the BNA method is sensitive to the effects of scopolamine on working memory and that it may potentially enable diagnosis and treatment assessment of dysfunctions associated with cholinergic deficiency.

  15. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine

    PubMed Central

    Wohleb, Eric S.; Wu, Min; Gerhard, Danielle M.; Taylor, Seth R.; Picciotto, Marina R.; Alreja, Meenakshi; Duman, Ronald S.

    2016-01-01

    Major depressive disorder (MDD) is a recurring psychiatric illness that causes substantial health and socioeconomic burdens. Clinical reports have revealed that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in individuals with MDD. Preclinical models suggest that these rapid antidepressant effects can be recapitulated with blockade of M1-type muscarinic acetylcholine receptors (M1-AChR); however, the cellular mechanisms underlying activity-dependent synaptic and behavioral responses to scopolamine have not been determined. Here, we demonstrate that the antidepressant-like effects of scopolamine are mediated by GABA interneurons in the medial prefrontal cortex (mPFC). Both GABAergic (GAD67+) interneurons and glutamatergic (CaMKII+) interneurons in the mPFC expressed M1-AChR. In mice, viral-mediated knockdown of M1-AChR specifically in GABAergic neurons, but not glutamatergic neurons, in the mPFC attenuated the antidepressant-like effects of scopolamine. Immunohistology and electrophysiology showed that somatostatin (SST) interneurons in the mPFC express M1-AChR at higher levels than parvalbumin interneurons. Moreover, knockdown of M1-AChR in SST interneurons in the mPFC demonstrated that M1-AChR expression in these neurons is required for the rapid antidepressant-like effects of scopolamine. These data indicate that SST interneurons in the mPFC are a promising pharmacological target for developing rapid-acting antidepressant therapies. PMID:27270172

  16. Enhancing the scopolamine production in transgenic plants of Atropa belladonna by overexpressing pmt and h6h genes.

    PubMed

    Wang, Xirong; Chen, Min; Yang, Chunxian; Liu, Xiaoqiang; Zhang, Lei; Lan, Xiaozhong; Tang, Kexuan; Liao, Zhihua

    2011-12-01

    Atropa belladonna is officially deemed as the commercial plant to produce scopolamine in China. In this study we report the simultaneous overexpression of two functional genes involved in biosynthesis of scopolamine, which encode the upstream key enzyme putrescine N-methyltransferase (PMT) and the downstream key enzyme hyoscyamine 6β-hydroxylase (H6H), respectively, in transgenic herbal plants Atropa belladonna. Analysis of gene expression profile indicated that both pmt and h6h were expressed at a higher level in transgenic lines, which would be favorable for biosynthesis of scopolamine. High-performance liquid chromatography result suggested that transgenic lines could produce higher accumulation of scopolamine at different levels compared with wild-type lines. Scopolamine content increased to 7.3-fold in transgenic line D9 compared with control lines. This study not only confirms that co-overexpression of pmt and h6h is an ideal method to improve the biosynthetic capacity of scopolamine but also successfully cultivates the transgenic line D9, which significantly enhanced the scopolamine accumulation. Our research can serve as an alternative choice to provide scopolamine resources for relative industry, which is more competitive than conventional market.

  17. Comparison of peripheral anticholinergic effects of antidepressants: dry mouth.

    PubMed

    Rafaelsen, O J; Clemmesen, L; Lund, H; Mikkelsen, P L; Bolwig, T G

    1981-01-01

    Twenty-one healthy volunteers were given single doses of placebo or antidepressants corresponding to average daily doses of patient medications. Spontaneous whole mouth and parotid salivation was measured two, six, and ten hours after drug administration in session 1; in session 2 after ten hours. The results indicate that a subdivision of antidepressants into four groups can be made according to inhibitory effect on salivation: (a) isocarboxazide and lithium citrate with no effect, (b) zimelidine and nomifensine with slight effect, (c) imipramine oxide and mianserin with moderate effect and (d) maprotiline, nortriptyline, clomipramine, imipramine, and amitriptyline with pronounced effect. Research implications and predictive value for new antidepressants are discussed.

  18. Clinical pharmacokinetics of drugs used to treat urge incontinence.

    PubMed

    Guay, David R P

    2003-01-01

    Urge incontinence (also known as overactive bladder) is a common form of urinary incontinence, occurring alone or as a component of mixed urinary incontinence, frequently together with stress incontinence. Because of the pathophysiology of urge incontinence, anticholinergic/antispasmodic agents form the cornerstone of therapy. Unfortunately, the pharmacological activity of these agents is not limited to the urinary tract, leading to systemic adverse effects that often promote nonadherence. Although the pharmacokinetics of flavoxate, propantheline, scopolamine, imipramine/desipramine, trospium chloride and propiverine are also reviewed here, only for oxybutynin and tolterodine are there adequate efficacy/tolerability data to support their use in urge incontinence. Oxybutynin is poorly absorbed orally (2-11% for the immediate-release tablet formulation). Controlled-release oral formulations significantly prolong the time to peak plasma concentration and reduce the degree of fluctuation around the average concentration. Significant absorption occurs after intravesical (bladder) and transdermal administration, although concentrations of the active N-desethyl metabolite are lower after transdermal compared with oral administration, possibly improving tolerability. Food has been found to significantly affect the absorption of one of the controlled-release formulations of oxybutynin, enhancing the rate of drug release. Oxybutynin is extensively metabolised, principally via N-demethylation mediated by the cytochrome P450 (CYP) 3A isozyme. The pharmacokinetics of tolterodine are dependent in large part on the pharmacogenomics of the CYP2D6 and 3A4 isozymes. In an unselected population, oral bioavailability of tolterodine ranges from 10% to 74% (mean 33%) whereas in CYP2D6 extensive metabolisers and poor metabolisers mean bioavailabilities are 26% and 91%, respectively. Tolterodine is metabolised via CYP2D6 to the active metabolite 5-hydroxymethyl-tolterodine and via CYP3A

  19. The effect of antimotion sickness drugs on habituation to motion

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Manno, B. R.; Odenheimer, R. C.; Bairnsfather, L. E.

    1986-01-01

    The mechanism which allows for increased exposure to motion and accelerates habituation is investigated. The responses of 12 male and female subjects between 18-30 years rotated once a day for 5 days on the Contraves Goerz rotating chair after receiving placebo, 10 mg d-amphetamine, 0.6 mg scopolamine with 5 mg d-amphetamine, and 1.0 mg scopolamine are studied. It is observed that with placebo the subjects performed 48 more head movements than untreated subjects, 118 more movements with d-amphetamine, 176 more with 0.6 mg scopolamine with d-amphetamine, and 186 more with 1.0 scopolamine. The data reveal that exposure to rotation increases tolerance from 88 head movements on day 2 to 159 on day 4 at 17.4 rpm and with placebo; 96 to 186 at 19.9 rpm with 10 mg d-amphetamine; 111 to 273 at 20.2 rpm with scopolamine with d-amphetamine, and 141 to 279 at 22.4 rpm with 1.0 mg scopolamine. It is noted that a combination of cholinergic blocking and norepinephrine activation action is most effective in preventing the development of motion sickness and habituation is due to the greater exposure to vestibular simulation permitted by the drugs.

  20. The effect of antimotion sickness drugs on habituation to motion

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Manno, B. R.; Odenheimer, R. C.; Bairnsfather, L. E.

    1986-01-01

    The mechanism which allows for increased exposure to motion and accelerates habituation is investigated. The responses of 12 male and female subjects between 18-30 years rotated once a day for 5 days on the Contraves Goerz rotating chair after receiving placebo, 10 mg d-amphetamine, 0.6 mg scopolamine with 5 mg d-amphetamine, and 1.0 mg scopolamine are studied. It is observed that with placebo the subjects performed 48 more head movements than untreated subjects, 118 more movements with d-amphetamine, 176 more with 0.6 mg scopolamine with d-amphetamine, and 186 more with 1.0 scopolamine. The data reveal that exposure to rotation increases tolerance from 88 head movements on day 2 to 159 on day 4 at 17.4 rpm and with placebo; 96 to 186 at 19.9 rpm with 10 mg d-amphetamine; 111 to 273 at 20.2 rpm with scopolamine with d-amphetamine, and 141 to 279 at 22.4 rpm with 1.0 mg scopolamine. It is noted that a combination of cholinergic blocking and norepinephrine activation action is most effective in preventing the development of motion sickness and habituation is due to the greater exposure to vestibular simulation permitted by the drugs.

  1. [Use of oral anticholinergic therapy in children under 1 years of age with high risk bladder].

    PubMed

    Luque Mialdea, R; Martín-Crespo, R; Hernández, E; Sánchez, O; Cañizo, A; Fernández, A; Aparicio, C; Blanco, T; Cebrían, J

    2005-01-01

    To assess the effectiveness and safety of the treatment with oral anticholinergic agents (Oxybutin clorure) in patients under 1 year old, and who aree carriers of high risk bladder secondary to neurological illness as well as no neurological one. Since 1989, we have indicated treatment with anticholinergic agents to 16 patients: 9 patients had neurogenic bladder secondary to: myelomeningocele (n=7) and sacrocoxigeal teratoma (n=2). Others 7 patients had non neurogenic bladder secondary to: posterior urethral valvulas (n=1), valvula-like syndrome (n=4), post-surgery of neonatal giant bladder diverticulum (n=1) and Prune-Belly syndrome (n=1). The urodinamic study was performed during the first six months of life, being "high risk bladder" defined according to the parameters of compliance vesical and pressure of leak at point (PER). Five of the patients showed neonatal cronic renal failure (CRF), who were treated by cutaneus temporary derivation. All patients at treatment with anticholinergic agents at a 0.2 mg/kg/day dose was established; other early adjunctive treatment prior to the closure of the urinary derivation in children with CRF(n=5); or as a part of the conservative treatment (n=3), alone or associate to intermittent bladder catheterization (IBC) (n=8). During the treatment with anticholinergic agents, the cardiac frequency was controlled by EKG registration in 6 patients, being the rest of the children clinicaly controled (skin colour, mouth dryness, cardiac frequency and intestinal function). In all the cases, the minimum duration of the treatment was one year, until the functional stabilization of the urinary tract. It is to underline the absence of secondary complications which would have caused the suspension or the reduction of the treatment at long term. Conventional studies of urologicals image and urodinamic studies, showed the stabilization of the urinary tract and also the preservation of kidney function and not only was demonstrated in those

  2. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets.

    PubMed

    Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

    2011-01-01

    Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH's intrinsic characteristics.

  3. A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

    PubMed Central

    Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

    2011-01-01

    Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

  4. Control of drooling using transdermal scopolamine skin patches. A case report.

    PubMed

    Mato Montero, Abigail; Limeres Posse, Jacobo; Tomás Carmona, Inmaculada; Fernández Feijoo, Javier; Diz Dios, Pedro

    2008-01-01

    Transdermal scopolamine has been shown to be very useful in the management of drooling, particularly in patients with neurological or neuropsychiatric disturbances or severe developmental disorders. In this paper, we present the case of a 24-year-old patient with a diagnosis of cerebral palsy and a severe problem of drooling, exacerbated by marked mandibular prognathism. After exclusion of other therapeutic alternatives, it was decided to use sustained-release transdermal scopolamine patches (Scopoderm TTS). This technique consists of the application every three days of a patch with 1.5 mg of scopolamine in the area of the mastoid apophysis; the patch releases a dose of 0.5 mg of the active substance over each 24 hour period. The patient underwent periodic clinical and laboratory follow-up over a period of three years, achieving satisfactory results with no significant undesirable effects.

  5. Lactucopicrin ameliorates oxidative stress mediated by scopolamine-induced neurotoxicity through activation of the NRF2 pathway.

    PubMed

    Venkatesan, Ramu; Subedi, Lalita; Yeo, Eui-Ju; Kim, Sun Yeou

    2016-10-01

    Cholinergic activity plays a vital role in cognitive function, and is reduced in individuals with neurodegenerative diseases. Scopolamine, a muscarinic cholinergic antagonist, has been employed in many studies to understand, identify, and characterize therapeutic targets for Alzheimer's disease (AD). Scopolamine-induced dementia is associated with impairments in memory and cognitive function, as seen in patients with AD. The current study aimed to investigate the molecular mechanisms underlying scopolamine-induced cholinergic neuronal dysfunction and the neuroprotective effect of lactucopicrin, an inhibitor of acetylcholine esterase (AChE). We investigated apoptotic cell death, caspase activation, generation of reactive oxygen species (ROS), mitochondrial dysfunction, and the expression levels of anti- and pro-apoptotic proteins in scopolamine-treated C6 cells. We also analyzed the expression levels of antioxidant enzymes and nuclear factor (erythroid-derived 2)-like 2 (NRF2) in C6 cells and neurite outgrowth in N2a neuroblastoma cells. Our results revealed that 1 h scopolamine pre-treatment induced cytotoxicity by increasing apoptotic cell death via oxidative stress-mediated caspase 3 activation and mitochondrial dysfunction. Scopolamine also downregulated the expression the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase, and the transcription factor NRF2. Lactucopicrin treatment protected C6 cells from scopolamine-induced toxicity by reversing the effects of scopolamine on those markers of toxicity. In addition, scopolamine attenuated the secretion of neurotrophic nerve growth factor (NGF) in C6 cells and neurite outgrowth in N2a cells. As expected, lactucopicrin treatment enhanced NGF secretion and neurite outgrowth. Our study is the first to show that lactucopicrin, a potential neuroprotective agent, ameliorates scopolamine-induced cholinergic dysfunction via NRF2 activation and subsequent expression of antioxidant enzymes.

  6. Scopolamine impairs behavioural function and arginine metabolism in the rat dentate gyrus.

    PubMed

    Knox, Logan T; Jing, Yu; Fleete, Michael S; Collie, Nicola D; Zhang, Hu; Liu, Ping

    2011-12-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss. It has been shown that the cholinergic neurotransmission deficit is one of the neurochemical characteristics of AD, and that L-arginine and its metabolites also play a prominent role in AD pathogenesis. Scopolamine, a non-selective muscarinic receptor antagonist, blocks cholinergic neurotransmission and impairs behavioural function, including learning and memory. This study investigated the effects of scopolamine on animals' behavioural performance and L-arginine metabolism in the hippocampus and prefrontal cortex. Rats were given intraperitoneal injections of scopolamine (0.8 mg/kg) or saline (1 ml/kg) and tested in the Y-maze, open field, water maze and elevated plus maze 30 min post-treatment. After completion of the behavioural testing, the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal cortex were harvested to measure the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and GABA. Scopolamine treated rats displayed reduced alternation and exploratory behaviour, increased swimming speed and impaired spatial learning and memory. There were significantly decreased NOS activity, increased arginase activity, and increased L-ornithine and putrescine levels in the DG, but not other regions examined, in the scopolamine treated rats as compared to the controls. These findings suggest that scopolamine impairs behavioural function and alters L-arginine metabolism in the DG sub-region of the hippocampus specifically. The underlying mechanisms of it remain to be explored further.

  7. Calotropis procera: A potential cognition enhancer in scopolamine and electroconvulsive shock-induced amnesia in rats

    PubMed Central

    Malabade, Rohit; Taranalli, Ashok D.

    2015-01-01

    Objectives: Present study evaluates the effect of Calotropis procera (Apocynaceae) dry latex on cognitive function in rats using scopolamine and electroconvulsive shock (ECS) induced amnesia model. Materials and Methods: Male Wistar rats were pretreated with 200, 400 and 800 mg/kg of C. procera dry latex in scopolamine-induced amnesia model. Dose showing maximum effect in cognitive performance was selected and further evaluated using scopolamine and ECS-induced amnesia model for its effect on neurochemical enzymes and cognitive performance. Acetylcholinesterase (AChE) activity, β amyloid1-42, and dopamine level were analyzed, while the cognitive performance was assessed by elevated plus maze, step-through passive avoidance test, and Morris water maze. Simultaneously, C. procera dry latex (25, 50, 100, 250, 500, and 1000 μg/mL) was screened for in vitro AChE inhibition assay. Results: Pretreatment with (200, 400 and 800 mg/kg) C. procera dry latex shows dose dependent increase in cognitive performance in scopolamine-induced amnesia. Further, pretreatment with the selected dose (800 mg/kg) showed significant improvement in transfer latency (P < 0.001, P < 0.01), escape latency (P < 0.05), time spent in target quadrant (P < 0.001) also significant decrease in AChE activity (P < 0.05), β amyloid1-42 level (P < 0.001), and increase in dopamine level (P < 0.01) in rat brain homogenate when compared with scopolamine and ECS disease control groups. IC50 for C. procera dry latex was found to be <1000 μg/mL. Conclusions: Pretreatment with C. procera dry latex (800 mg/kg) produced significant cognition enhancement by improving cognitive performance and decreasing the marker neurochemical enzyme activity in scopolamine and ECS-induced amnesia model. PMID:26288476

  8. Calotropis procera: A potential cognition enhancer in scopolamine and electroconvulsive shock-induced amnesia in rats.

    PubMed

    Malabade, Rohit; Taranalli, Ashok D

    2015-01-01

    Present study evaluates the effect of Calotropis procera (Apocynaceae) dry latex on cognitive function in rats using scopolamine and electroconvulsive shock (ECS) induced amnesia model. Male Wistar rats were pretreated with 200, 400 and 800 mg/kg of C. procera dry latex in scopolamine-induced amnesia model. Dose showing maximum effect in cognitive performance was selected and further evaluated using scopolamine and ECS-induced amnesia model for its effect on neurochemical enzymes and cognitive performance. Acetylcholinesterase (AChE) activity, β amyloid1-42, and dopamine level were analyzed, while the cognitive performance was assessed by elevated plus maze, step-through passive avoidance test, and Morris water maze. Simultaneously, C. procera dry latex (25, 50, 100, 250, 500, and 1000 μg/mL) was screened for in vitro AChE inhibition assay. Pretreatment with (200, 400 and 800 mg/kg) C. procera dry latex shows dose dependent increase in cognitive performance in scopolamine-induced amnesia. Further, pretreatment with the selected dose (800 mg/kg) showed significant improvement in transfer latency (P < 0.001, P < 0.01), escape latency (P < 0.05), time spent in target quadrant (P < 0.001) also significant decrease in AChE activity (P < 0.05), β amyloid1-42 level (P < 0.001), and increase in dopamine level (P < 0.01) in rat brain homogenate when compared with scopolamine and ECS disease control groups. IC50 for C. procera dry latex was found to be <1000 μg/mL. Pretreatment with C. procera dry latex (800 mg/kg) produced significant cognition enhancement by improving cognitive performance and decreasing the marker neurochemical enzyme activity in scopolamine and ECS-induced amnesia model.

  9. Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats

    PubMed Central

    Giménez De Béjar, Verónica; Caballero Bleda, María; Popović, Natalija; Popović, Miroljub

    2017-01-01

    Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0.5, 1.0, 2.5, 5.0, 10, or 20 mg/kg i.p.) as well as the interaction between scopolamine and verapamil on memory consolidation in the step-through passive avoidance task, in Wistar rats. Our results showed that verapamil (1.0 and 2.5 mg/kg) administered immediately after the acquisition task significantly increased the latency of the passive avoidance response, on the 48 h retested trial, improving memory consolidation. On the other hand, verapamil in a dose of 5 mg/kg, that per se does not affect memory consolidation, significantly reversed the memory consolidation improvement induced by scopolamine (1 mg/kg, i.p., administered immediately after verapamil treatment) but did not change the passive avoidance response in rats treated by an ineffective dose of scopolamine (30 mg/kg). In conclusion, the present data suggest that (1) the post-training administration of verapamil, dose-dependently, improves the passive avoidance response; (2) verapamil, in ineffective dose, abolished the improvement of memory consolidation effect of scopolamine; and (3) exists interaction between cholinergic muscarinic receptors and calcium homeostasis-related mechanisms in the consolidation of emotional memory. PMID:28878678

  10. Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats.

    PubMed

    Giménez De Béjar, Verónica; Caballero Bleda, María; Popović, Natalija; Popović, Miroljub

    2017-01-01

    Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0.5, 1.0, 2.5, 5.0, 10, or 20 mg/kg i.p.) as well as the interaction between scopolamine and verapamil on memory consolidation in the step-through passive avoidance task, in Wistar rats. Our results showed that verapamil (1.0 and 2.5 mg/kg) administered immediately after the acquisition task significantly increased the latency of the passive avoidance response, on the 48 h retested trial, improving memory consolidation. On the other hand, verapamil in a dose of 5 mg/kg, that per se does not affect memory consolidation, significantly reversed the memory consolidation improvement induced by scopolamine (1 mg/kg, i.p., administered immediately after verapamil treatment) but did not change the passive avoidance response in rats treated by an ineffective dose of scopolamine (30 mg/kg). In conclusion, the present data suggest that (1) the post-training administration of verapamil, dose-dependently, improves the passive avoidance response; (2) verapamil, in ineffective dose, abolished the improvement of memory consolidation effect of scopolamine; and (3) exists interaction between cholinergic muscarinic receptors and calcium homeostasis-related mechanisms in the consolidation of emotional memory.

  11. Scopolamine in Brugmansia suaveolens (Solanaceae): defense, allocation, costs, and induced response.

    PubMed

    Alves, Marcos Nopper; Sartoratto, Adilson; Trigo, José Roberto

    2007-02-01

    Brugmansia suaveolens (Solanaceae) contains tropane alkaloids (TAs), which can act as chemical defenses. Selective pressures might modulate the allocation of alkaloids within the plant, as postulated by optimal-defense theory. By tracing scopolamine, the most abundant TA in this species, we found that scopolamine in an artificial diet, in concentrations similar to those in leaves of B. suaveolens, increased mortality and prolonged developmental time of the larvae of the generalist noctuid moth Spodoptera frugiperda. A diet of undamaged leaves of B. suaveolens also showed a large negative effect on the growth of larvae of S. frugiperda compared to a diet of leaves of Ricinus communis, a species that did not have negative effects on this moth; more valuable plant parts, such as young leaves, flowers, and unripe fruits with seeds, have higher scopolamine concentrations than other tissues; leaves of B. suaveolens increase their content of scopolamine after artificial damage. The highest induction was found 24 hr after the damage, and after that, scopolamine content decreased to constitutive levels. This increase represented a cost, because in another experiment, a treatment with methyl jasmonate, an elicitor hormone, increased scopolamine production 9.5-fold and decreased leaf growth 2.3-fold; a diet of artificially damaged leaves of B. suaveolens showed a negative effect on the growth of larvae of S. furgiperda compared to undamaged leaves, suggesting that damage by herbivores induces resistance. Our data are in line with the optimal-defense theory, but experiments in the field with herbivores that share an evolutionary history with B. suaveolens must be undertaken to understand the dynamics of TA allocation in response to herbivory.

  12. Willughbeia cochinchinensis prevents scopolamine-induced deficits in memory, spatial learning, and object recognition in rodents.

    PubMed

    Van Can, Mao; Tran, Anh Hai; Pham, Dam Minh; Dinh, Bao Quoc; Van Le, Quan; Van Nguyen, Ba; Thi Nguyen, Mai Thanh; Nguyen, Hai Xuan; Nguyen, Nhan Trung; Nishijo, Hisao

    2017-06-23

    Willughbeia cochinchinensis (WC) has been used in Vietnamese traditional medicine for the treatment of dementia as well as diarrhea, heartburn, and cutaneous abscess and as a diuretic. Alzheimer's disease (AD) is one of the most prevalent diseases in elderly individuals. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors have been widely used to treat patients with AD. In the present study, we investigated anti-AChE and anti-BChE activities of a natural product, WC, for its potential applications in therapies to prevent/treat dementia. First, compounds extracted from WC were tested for their AChE and BChE inhibitory activities in vitro. Second, in vivo behavioral experiments were performed to investigate the effects of WC at doses of 100, 150, and 200mg/kg on scopolamine (1.5mg/kg)-induced memory and cognitive deficits in mice. The behavior of mice treated with and without WC and/or scopolamine was tested using the Y-maze, Morris water maze, and novel object recognition task. The results of the in vitro assay demonstrated anti-AChE and anti-BChE activities of the compounds extracted from WC. The results of behavioral experiments showed that the administration of WC prevented 1) scopolamine-induced decrease in spontaneous alternation (%) behavior in the Y-maze, 2) scopolamine-induced deficits in spatial learning and memory in the Morris water maze, and 3) scopolamine-induced deficits in novel object recognition. These results indicate that WC prevents cognitive and memory deficits induced by scopolamine injection. Our findings suggest that WC may represent a novel candidate for the treatment of memory and cognitive deficits in humans with dementia. Copyright © 2017. Published by Elsevier B.V.

  13. Reducing prescribing of highly anticholinergic antidepressants for elderly people: randomised trial of group versus individual academic detailing

    PubMed Central

    van Eijk, Martine E C; Avorn, Jerry; Porsius, Arijan J; de Boer, Anthonius

    2001-01-01

    Objective To compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people. Design Randomised controlled trial with three arms (individual visits, group visits, and a control arm). Setting Southwest Netherlands. Participants 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a database covering all prescriptions to people covered by national health insurance in the area (about 240 000). Intervention All general practitioners and pharmacists in both intervention arms were offered two educational visits. For physicians in groups randomised to the individual visit arm, 43 of 70 general practitioners participated; in the group visit intervention arm, five of seven groups (41 of 52 general practitioners) participated. Main outcome measures Numbers of elderly people (⩾60 years) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants. Results An intention to treat analysis found a 26% reduction in the rate of starting highly anticholinergic antidepressants in elderly people (95% confidence interval −4% to 48%) in the individual intervention arm and 45% (8% to 67%) in the group intervention arm. The use of less anticholinergic antidepressants increased by 40% (6% to 83%) in the individual intervention arm and 29% (−7% to 79%) in the group intervention arm. Conclusions Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people. These approaches are practical means to improve prescribing by continuing medical education. PMID:11250852

  14. [Role of anticholinergic agents in acute bronchiolitis in infants].

    PubMed

    Milner, A

    1995-01-01

    There is almost universal agreement that neither beta 2-agonists, theophyllin nor steroids, given either by inhalation or systemically, have any effect on lung function in acute bronchiolitis of infancy. As ipratropium bromide appears to be a more effective bronchodilator drug than beta 2-stimulants in the first year of life, a study was set up to investigate its possible role in bronchiolitis. Diagnostic requirements for inclusion in the study were tachypnoea, hyperinflation recession, and the presence of fine crepitations on auscultation with a chest X-ray which excluded either heart failure or gross pneumonia. Twenty-five infants were recruited in the preliminary study. A respiratory jacket and water filled oesophageal catheter (feeding tube) were used to measure the work of breathing per minute and per litre of expired gases. After baseline readings the infants received salbutamol (2.5 mg), ipratropium bromide (250 micrograms) or placebo in 2 ml volumes using a standard nebuliser. The salbutamol and water were associated with an increase in the work of breathing of 4% and 22% respectively. The ipratropium therapy led to a fall of 18% with a significant response in 6 of 15 infants studied. Following these encouraging results, a double blind study was set up assessing the effects of nebulised ipratropium bromide (250 micrograms) and nebulised saline given every 6 hours to 66 infants admitted to the ward with acute bronchiolitis. Response to therapy was determined using symptom scores and need for nebulised therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Mitochondrial involvement in memory impairment induced by scopolamine in rats.

    PubMed

    Wong-Guerra, Maylin; Jiménez-Martin, Javier; Pardo-Andreu, Gilberto L; Fonseca-Fonseca, Luis A; Souza, Diogo O; de Assis, Adriano M; Ramirez-Sanchez, Jeney; Del Valle, Roberto Menéndez-Soto; Nuñez-Figueredo, Yanier

    2017-07-01

    Scopolamine (SCO) administration to rats induces molecular features of AD and other dementias, including impaired cognition, increased oxidative stress, and imbalanced cholinergic transmission. Although mitochondrial dysfunction is involved in different types of dementias, its role in cognitive impairment induced by SCO has not been well elucidated. The aim of this work was to evaluate the in vivo effect of SCO on different brain mitochondrial parameters in rats to explore its neurotoxic mechanisms of action. Saline (Control) or SCO (1 mg/kg) was administered intraperitoneally 30 min prior to neurobehavioral and biochemical evaluations. Novel object recognition and Y-maze paradigms were used to evaluate the impact on memory, while redox profiles in different brain regions and the acetylcholinesterase (AChE) activity of the whole brain were assessed to elucidate the amnesic mechanism of SCO. Finally, the effects of SCO on brain mitochondria were evaluated both ex vivo and in vitro, the latter to determine whether SCO could directly interfere with mitochondrial function. SCO administration induced memory deficit, increased oxidative stress, and increased AChE activities in the hippocampus and prefrontal cortex. Isolated brain mitochondria from rats administered with SCO were more vulnerable to mitochondrial swelling, membrane potential dissipation, H2O2 generation and calcium efflux, all likely resulting from oxidative damage. The in vitro mitochondrial assays suggest that SCO did not affect the organelle function directly. In conclusion, the present results indicate that SCO induced cognitive dysfunction and oxidative stress may involve brain mitochondrial impairment, an important target for new neuroprotective compounds against AD and other dementias.

  16. D-cycloserine in Prelimbic Cortex Reverses Scopolamine-Induced Deficits in Olfactory Memory in Rats

    PubMed Central

    Portero-Tresserra, Marta; Cristóbal-Narváez, Paula; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

    2013-01-01

    A significant interaction between N-methyl-D-aspartate (NMDA) and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS), a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP)-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC). Thus, in experiment 1, DCS (10 µg/site) was infused prior to acquisition of odor discrimination (ODT) and social transmission of food preference (STFP), which have been previously characterized as paradigms sensitive to PLC muscarinic blockade. Immediately after learning such tasks, SCOP was injected (20 µg/site) and the effects of both drugs (alone and combined) were tested in 24-h retention tests. To assess whether DCS effects may depend on the difficulty of the task, in the STFP the rats expressed their food preference either in a standard two-choice test (experiment 1) or a more challenging three-choice test (experiment 2). The results showed that bilateral intra-PLC infusions of SCOP markedly disrupted the ODT and STFP memory tests. Additionally, infusions of DCS alone into the PLC enhanced ODT but not STFP retention. However, the DCS treatment reversed SCOP-induced memory deficits in both tasks, and this effect seemed more apparent in ODT and 3-choice STFP. Such results support the interaction between the glutamatergic and the cholinergic systems in the PLC in such a way that positive modulation of the NMDA receptor/channel, through activation of the glycine binding site, may compensate dysfunction of muscarinic neurotransmission involved in stimulus-reward and relational learning tasks. PMID:23936452

  17. Lycium barbarum Polysaccharides Prevent Memory and Neurogenesis Impairments in Scopolamine-Treated Rats

    PubMed Central

    Chen, Jinzhong; Yi, Xin; Nie, Dekang; Sun, Xiaohui; Qin, Jianbing; Tian, Meiling; Jin, Guohua; Zhang, Xinhua

    2014-01-01

    Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis. PMID:24505383

  18. Lycium barbarum polysaccharides prevent memory and neurogenesis impairments in scopolamine-treated rats.

    PubMed

    Chen, Weiwei; Cheng, Xiang; Chen, Jinzhong; Yi, Xin; Nie, Dekang; Sun, Xiaohui; Qin, Jianbing; Tian, Meiling; Jin, Guohua; Zhang, Xinhua

    2014-01-01

    Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis.

  19. Temporary cognitive impairment related to administration of newly developed anticholinergic medicines for overactive bladder: two case reports.

    PubMed

    Shiota, Takako; Torimoto, Kazumasa; Momose, Hitoshi; Nakamuro, Takuya; Mochizuki, Hiroshi; Kumamoto, Hiromi; Hirayama, Akihide; Fujimoto, Kiyohide

    2014-09-25

    Cognitive impairment is one of the side effects of using anticholinergic medicines for overactive bladder; however, its incidence has not been fully reported. We experienced two elderly Japanese patients with overactive bladder who had temporary cognitive impairment caused by anticholinergic medicines. The first case was a 79-year-old female patient to whom imidafenacin (0.2 mg) was administered daily to control her frequent micturition and urgency. She was taking the following medicines: etizolam, triazolam, captopril, bisoprolol, and amlodipine besylate. Her Hasegawa dementia rating scale-revised was impaired from 26/30 to 17/30 and recovered to 25/30 after the imidafenacin treatment was stopped. The second case was an 82-year-old female patient to whom imidafenacin (0.2 mg) was administered daily for frequent micturition and urgency. She was taking the following medicines: losartan potassium and clenbuterol. Her Hasegawa dementia rating scale-revised decreased from 28/30 to 19/30 and recovered to 24/30 after the imidafenacin treatment was stopped. In our patients who were taking multiple medicines, there is a possibility that medicines other than anticholinergics may have caused cognitive impairment. We need to keep in mind that many elderly people take multiple medicines because of comorbidity. Anticholinergic medicines can cause cognitive impairment in elderly people, and attention should be paid to cognition when elderly overactive bladder patients are treated with anticholinergic medicines.

  20. Auraptene consolidates memory, reverses scopolamine-disrupted memory in passive avoidance task, and ameliorates retention deficits in mice

    PubMed Central

    Tabrizian, Kaveh; Yaghoobi, Najmeh Sadat; Iranshahi, Mehrdad; Shahraki, Jafar; Rezaee, Ramin; Hashemzaei, Mahmoud

    2015-01-01

    Objective(s): Auraptene (7-geranyloxycoumarin) (AUR), from Citrus species has shown anti-inflammatory, neuroprotective, and acetylcholinesterase (AChE) and beta-secretase inhibitory effects. Scopolamine is a nonselective muscarinic receptor antagonist which causes short-term memory impairments and is used for inducing animal model of Alzheimer’s disease (AD). This research aimed to investigate the effect of AUR on scopolamine-induced avoidance memory retention deficits in step-through task in mice. Materials and Methods: The effect of four-day pre-training injections of AUR (50, 75, and 100 mg/kg, subcutaneous (SC)) and scopolamine (1 mg/kg, IP), and their co-administration on avoidance memory retention in step-through passive avoidance task, was investigated by measuring the latency to enter to the dark chamber. Results: Pre-training administration of AUR caused significant increase in step-through latency in comparison with control group, 48, 96, and 168 hr after training trial. The findings of this study showed that scopolamine (1 mg/kg, IP, for four consecutive days) impaired passive avoidance memory retention compared to saline-treated animals. Step-through passive avoidance task results showed that AUR markedly reversed scopolamine-induced avoidance memory retention impairments, 24 and 168 hr after training trial in step-through task. Conclusion: Results from co-administration of AUR and scopolamine showed that AUR reversed scopolamine-induced passive avoidance memory retention impairments. PMID:26730337

  1. Efficacy and Tolerability of Anticholinergics in Korean Children with Overactive Bladder: A Multicenter Retrospective Study

    PubMed Central

    2014-01-01

    We investigated the efficacy and tolerability of various anticholinergics in Korean children with non-neurogenic overactive bladder (OAB). A total of 326 children (males:females= 157:169) aged under 18 yr (mean age 7.3±2.6 yr) who were diagnosed with OAB from 2008 to 2011 were retrospectively reviewed. The mean duration of OAB symptoms before anticholinergic treatment was 16.9±19.0 months. The mean duration of medication was 5.6±7.3 months. Urgency urinary incontinence episodes per week decreased from 1.9±3.1 to 0.4±1.5 times (P<0.001). The median voiding frequency during daytime was decreased from 9.2±5.4 to 6.3±4.2 times (P<0.001). According to 3-day voiding diaries, the maximum and average bladder capacity were increased from 145.5±66.9 to 196.8±80.3 mL and from 80.8±39.6 to 121.8±56.5 mL, respectively (P<0.001). On uroflowmetry, maximum flow rate was increased from 17.6±8.4 to 20.5±8.2 mL/sec (P<0.001). Adverse effects were reported in 14 (4.3%) children and six children (1.8%) discontinued medication due to adverse effects. Our results indicate that anticholinergics are effective to improve OAB symptoms and tolerability was acceptable without severe complications in children. PMID:25408588

  2. Efficacy and tolerability of anticholinergics in Korean children with overactive bladder: a multicenter retrospective study.

    PubMed

    Park, Se Jin; Pai, Ki Soo; Kim, Jun Mo; Park, Kwanjin; Kim, Kun Suk; Song, Sang Hoon; Park, Sungchan; Kim, Sun-Ouck; Ryu, Dong Soo; Baek, Minki; Lee, Sang Don; Lee, Jung Won; Im, Young Jae; Han, Sang Won; Chung, Jae Min; Cho, Min Hyun; Ha, Tae-Sun; Cho, Won Yeol; Suh, Hong Jin

    2014-11-01

    We investigated the efficacy and tolerability of various anticholinergics in Korean children with non-neurogenic overactive bladder (OAB). A total of 326 children (males:females= 157:169) aged under 18 yr (mean age 7.3±2.6 yr) who were diagnosed with OAB from 2008 to 2011 were retrospectively reviewed. The mean duration of OAB symptoms before anticholinergic treatment was 16.9±19.0 months. The mean duration of medication was 5.6±7.3 months. Urgency urinary incontinence episodes per week decreased from 1.9±3.1 to 0.4±1.5 times (P<0.001). The median voiding frequency during daytime was decreased from 9.2±5.4 to 6.3±4.2 times (P<0.001). According to 3-day voiding diaries, the maximum and average bladder capacity were increased from 145.5±66.9 to 196.8±80.3 mL and from 80.8±39.6 to 121.8±56.5 mL, respectively (P<0.001). On uroflowmetry, maximum flow rate was increased from 17.6±8.4 to 20.5±8.2 mL/sec (P<0.001). Adverse effects were reported in 14 (4.3%) children and six children (1.8%) discontinued medication due to adverse effects. Our results indicate that anticholinergics are effective to improve OAB symptoms and tolerability was acceptable without severe complications in children.

  3. Effects of electroacupuncture on overactive bladder refractory to anticholinergics: a single-blind randomised controlled trial.

    PubMed

    Zhang, Jie; Cheng, Wei; Cai, Mingming

    2015-10-01

    To investigate the clinical effects and safety of electroacupuncture (EA) in the treatment of overactive bladder (OAB) refractory to first-line anticholinergic treatment. Women diagnosed with OAB who were refractory to first-line anticholinergic treatment were referred for EA therapy. 50 women enrolled in this single-blind randomised controlled trial and were randomised 1:1 to EA or sham EA (SEA). The EA and SEA groups were treated with 30 sessions (5 sessions a week for 6 weeks), and each session lasted 30 min. OAB symptom scores (OABSS), King's Health Questionnaire scores (KHQ) and urodynamic parameters were used to assess treatment effects. Safety was also evaluated. 45 women completed all aspects of the study (23 in the EA group and 22 in the SEA group). The OABSS and KHQ showed statistically significant improvements in the EA group compared with the SEA group after 6 weeks of treatment (p<0.05). There were no statistical differences in the maximum flow rate and postvoid residual (p>0.05), but there were statistical improvements in the first sensation of bladder filling, first urge to void and maximum cystometric capacity (p<0.05) in the EA group compared with the SEA group. No serious adverse events occurred in either group. EA appears to be an effective, safe and minimally invasive treatment for women with OAB. Further studies with longer follow-up are needed to evaluate whether it could be a therapeutic option for OAB refractory to treatment with anticholinergics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Prejudices in pharmacology and pharmacotherapy. The so-called anticholinergic effect of antidepressants.

    PubMed

    Bein, H J

    1977-09-01

    Imipramine and similarly acting compounds provoke a number of undesired reactions usually classified as so-called anticholinergic effects. Instances of dry mouth, disturbance of micturition and tachycardia are regularly quoted in the literature. It is contended that these effects are not necessarily due to inhibition of the vagal system, but preferentially attributable to increased activity of the sympathetic system, predominantly mediated by the beta- or the alpha-adrenergic receptors, depending on the organ affected. This hypothesis is not only theoretically interesting, but also of practical clinical significance with regard to possible remedies.

  5. Rapid antidepressant actions of scopolamine: Role of medial prefrontal cortex and M1-subtype muscarinic acetylcholine receptors.

    PubMed

    Navarria, Andrea; Wohleb, Eric S; Voleti, Bhavya; Ota, Kristie T; Dutheil, Sophie; Lepack, Ashley E; Dwyer, Jason M; Fuchikami, Manabu; Becker, Astrid; Drago, Filippo; Duman, Ronald S

    2015-10-01

    Clinical studies demonstrate that scopolamine, a non-selective muscarinic acetylcholine receptor (mAchR) antagonist, produces rapid therapeutic effects in depressed patients, and preclinical studies report that the actions of scopolamine require glutamate receptor activation and the mechanistic target of rapamycin complex 1 (mTORC1). The present study extends these findings to determine the role of the medial prefrontal cortex (mPFC) and specific muscarinic acetylcholine receptor (M-AchR) subtypes in the actions of scopolamine. The administration of scopolamine increases the activity marker Fos in the mPFC, including the infralimbic (IL) and prelimbic (PrL) subregions. Microinfusions of scopolamine into either the IL or the PrL produced significant antidepressant responses in the forced swim test, and neuronal silencing of IL or PrL blocked the antidepressant effects of systemic scopolamine. The results also demonstrate that the systemic administration of a selective M1-AChR antagonist, VU0255035, produced an antidepressant response and stimulated mTORC1 signaling in the PFC, similar to the actions of scopolamine. Finally, we used a chronic unpredictable stress model as a more rigorous test of rapid antidepressant actions and found that a single dose of scopolamine or VU0255035 blocked the anhedonic response caused by CUS, an effect that requires the chronic administration of typical antidepressants. Taken together, these findings indicate that mPFC is a critical mediator of the behavioral actions of scopolamine and identify the M1-AChR as a therapeutic target for the development of novel and selective rapid-acting antidepressants.

  6. Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment.

    PubMed

    Singh, Padmanabh; Konar, Arpita; Kumar, Ashish; Srivas, Sweta; Thakur, Mahendra K

    2015-08-01

    The amnesic potential of scopolamine is well manifested through synaptic plasticity gene expression changes and behavioral paradigms of memory impairment. However, the underlying mechanism remains obscure and consequently ideal therapeutic target is lacking. In this context, chromatin-modifying enzymes, which regulate memory gene expression changes, deserve major attention. Therefore, we analyzed the expression of chromatin-modifying enzymes and recovery potential of enzyme modulators in scopolamine-induced amnesia. Scopolamine administration drastically up-regulated DNA methyltransferases (DNMT1) and HDAC2 expression while CREB-binding protein (CBP), DNMT3a and DNMT3b remained unaffected. HDAC inhibitor sodium butyrate and DNMT inhibitor Aza-2'deoxycytidine recovered scopolamine-impaired hippocampal-dependent memory consolidation with concomitant increase in the expression of synaptic plasticity genes Brain-derived neurotrophic factor (BDNF) and Arc and level of histone H3K9 and H3K14 acetylation and decrease in DNA methylation level. Sodium butyrate showed more pronounced effect than Aza-2'deoxycytidine and their co-administration did not exhibit synergistic effect on gene expression. Taken together, we showed for the first time that scopolamine-induced up-regulation of chromatin-modifying enzymes, HDAC2 and DNMT1, leads to gene expression changes and consequent decline in memory consolidation. Our findings on the action of scopolamine as an epigenetic modulator can pave a path for ideal therapeutic targets. We propose the following putative pathway for scopolamine-mediated memory impairment; scopolamine up-regulates hippocampal DNMT1 and HDAC2 expression, induces methylation and deacetylation of BDNF and Arc promoter, represses gene expression and eventually impairs memory consolidation. On the other hand, Aza-2 and NaB inhibit DNMT1 and HDAC2 respectively, up-regulate BDNF and Arc expression and recover memory consolidation. We elucidate the action of

  7. Modulation of adenosine signaling prevents scopolamine-induced cognitive impairment in zebrafish.

    PubMed

    Bortolotto, Josiane Woutheres; Melo, Gabriela Madalena de; Cognato, Giana de Paula; Vianna, Mônica Ryff Moreira; Bonan, Carla Denise

    2015-02-01

    Adenosine, a purine ribonucleoside, exhibits neuromodulatory and neuroprotective effects in the brain and is involved in memory formation and cognitive function. Adenosine signaling is mediated by adenosine receptors (A1, A2A, A2B, and A3); in turn, nucleotide and nucleoside-metabolizing enzymes and adenosine transporters regulate its levels. Scopolamine, a muscarinic cholinergic receptor antagonist, has profound amnesic effects in a variety of learning paradigms and has been used to induce cognitive deficits in animal models. This study investigated the effects of acute exposure to caffeine (a non-selective antagonist of adenosine receptors A1 and A2A), ZM 241385 (adenosine receptor A2A antagonist), DPCPX (adenosine receptor A1 antagonist), dipyridamole (inhibitor of nucleoside transporters) and EHNA (inhibitor of adenosine deaminase) in a model of pharmacological cognitive impairment induced by scopolamine in adult zebrafish. Caffeine, ZM 241385, DPCPX, dipyridamole, and EHNA were acutely administered independently via i.p. in zebrafish, followed by exposure to scopolamine dissolved in tank water (200μM). These compounds prevented the scopolamine-induced amnesia without impacting locomotor activity or social interaction. Together, these data support the hypothesis that adenosine signaling may modulate memory processing, suggesting that these compounds present a potential preventive strategy against cognitive impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish.

    PubMed

    Richetti, S K; Blank, M; Capiotti, K M; Piato, A L; Bogo, M R; Vianna, M R; Bonan, C D

    2011-02-02

    Demographic aging gives rise to a growing population with age-associated behavioral and cognitive deficits that may be associated at least partially to the increasing prevalence of neurodegenerative disorders, such as Alzheimer's disease (AD). In this disease, it has been observed a decrease in the cholinergic system, which is crucial to memory formation. Scopolamine-induced amnesic effect, through the disruption of the cholinergic neurotransmission, is one of the approaches used to investigate the mechanisms involved in cognitive impairment observed in AD. The aim of our study was to investigate the potential protective role of quercetin and rutin against scopolamine-induced inhibitory avoidance memory deficits in zebrafish. Scopolamine (200 μM dissolved in the tank water for 1h) given pre-training hindered memory formation while both quercetin and rutin pretreatments (50mg/kg, single injection, i.p.) prevented the scopolamine-induced amnesia. None of the compounds affected zebrafish general locomotor activity. Together, these results contribute to the increase of the knowledge about plant compounds applicability as medicines to prevent and treat neurodegenerative diseases, like Alzheimer's disease. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Amnesia of Inhibitory Avoidance by Scopolamine Is Overcome by Previous Openfield Exposure

    ERIC Educational Resources Information Center

    Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge A.; Jerusalinsky, Diana A.

    2014-01-01

    The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two…

  10. Gongjin-Dan Enhances Hippocampal Memory in a Mouse Model of Scopolamine-Induced Amnesia

    PubMed Central

    Lee, Jin-Seok; Hong, Sung-Shin; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Lee, Sam-Keun; Son, Chang-Gue

    2016-01-01

    We evaluated the neuropharmacological effects of Gongjin-Dan (GJD) on the memory impairment caused by scopolamine injection. BALB/c mice were orally treated with GJD (100, 200, or 400 mg/kg, daily) or tacrine (THA, 10 mg/kg) for 10 days, and scopolamine (2 mg/kg) was injected intraperitoneally. The radial arm maze and passive avoidance tests were performed to evaluate the animal’s learning and memory. Scopolamine increased the task completing time, the number of total errors (reference and working memory error) in the radial arm maze task, and the latency time in the passive avoidance test, which were significantly ameliorated by treatment with GJD. The GJD treatment also attenuated the scopolamine-induced hyperactivation of acetylcholinesterase activity, and suppression of the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and their receptors in the hippocampus. These effects of GJD were supported by both the doublecortin (DCX)-positive staining and Nissl staining, which were used to measure hippocampal neurogenesis and atrophy, respectively. These findings strongly suggest that GJD exerts a potent anti-amnesic effect, and its underlying mechanism might involve the modulation of cholinergic activity. PMID:27483466

  11. Ameliorating effect of lyophilized extract of Butea frondosa leaves on scopolamine-induced amnesia in rats.

    PubMed

    Malik, Jai; Kumar, Munish; Deshmukh, Rahul; Kumar, Puneet

    2013-02-01

    Butea frondosa (BF) Roxb. & Koen. (syn. B. monosperma Lam.) (Fabaceae) leaves have been used in folklore medicine for the treatment of diabetes, conjunctivitis, gastrointestinal tract, and central nervous system disorders such as anxiety, amnesia, etc. To evaluate the effect of lyophilized hydroalcoholic extract of BF leaves (BFLE) at 100, 200 and 400 mg/kg, p.o., for its memory enhancing activity against scopolamine-induced amnesia in rats. Antiamnesic effect of the BFLE was evaluated using Morris water maze and object recognition test models. The effect of BFLE on acetylcholinesterase activity and malondialdehyde and glutathione levels were also evaluated in brain homogenate. BFLE ameliorates scopolamine-induced amnesia in both the models with maximum effect at 400 mg/kg. BFLE (400 mg/kg) decreased escape latency and increased time spent in target quadrant (24.2 and 42.5 s, respectively) in comparison to scopolamine (82 and 18.2 s, respectively) in the Morris water maze task. In the object recognition test, BFLE produced significant increase in ability to discriminate between novel and familiar objects. The highest investigated dose of BFLE (400 mg/kg), produced a significant decrease in acetylcholinesterase activity and malondialdehyde levels, and improves glutathione levels in comparison to scopolamine. Moreover, this effect of BFLE at 400 mg/kg was comparable to that of standard, donepezil. BFLE exhibited significant antiamnesic activity in rats thereby validating its folklore use.

  12. Gongjin-Dan Enhances Hippocampal Memory in a Mouse Model of Scopolamine-Induced Amnesia.

    PubMed

    Lee, Jin-Seok; Hong, Sung-Shin; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Lee, Sam-Keun; Son, Chang-Gue

    2016-01-01

    We evaluated the neuropharmacological effects of Gongjin-Dan (GJD) on the memory impairment caused by scopolamine injection. BALB/c mice were orally treated with GJD (100, 200, or 400 mg/kg, daily) or tacrine (THA, 10 mg/kg) for 10 days, and scopolamine (2 mg/kg) was injected intraperitoneally. The radial arm maze and passive avoidance tests were performed to evaluate the animal's learning and memory. Scopolamine increased the task completing time, the number of total errors (reference and working memory error) in the radial arm maze task, and the latency time in the passive avoidance test, which were significantly ameliorated by treatment with GJD. The GJD treatment also attenuated the scopolamine-induced hyperactivation of acetylcholinesterase activity, and suppression of the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and their receptors in the hippocampus. These effects of GJD were supported by both the doublecortin (DCX)-positive staining and Nissl staining, which were used to measure hippocampal neurogenesis and atrophy, respectively. These findings strongly suggest that GJD exerts a potent anti-amnesic effect, and its underlying mechanism might involve the modulation of cholinergic activity.

  13. Neuroprotective effects of polygalacic acid on scopolamine-induced memory deficits in mice.

    PubMed

    Guo, Changrun; Shen, Jinyang; Meng, Zhaoqing; Yang, Xiaolin; Li, Fei

    2016-02-15

    Polygala tenuifolia Willd is a Traditional Chinese Medicine used for the treatment of learning and memory deficits. Triterpenoid saponins, the main bioactive compounds of Polygala tenuifolia Willd, are easily hydrolyzed to polygalacic acid (PA). The present study was undertaken to investigate the neuroprotective effects of PA on scopolamine-induced cognitive dysfunction and to elucidate its underlying mechanisms of action. PA (3, 6, and 12 mg/kg) was administered orally to mice for fourteen days, and scopolamine (1 mg/kg) was injected intraperitoneally for fourteen days to induce memory impairment. Memory-related behaviors were evaluated using the Morris water maze. Cholinergic and neuroinflammatory activities were measured in brain tissue. Superoxide dismutase activities, malondialdehyde and reduced glutathione contents were also measured in the brains. Treatment with scopolamine significantly increased the escape latency time, decreased the number of crossings, and shortened the time spent in the target quadrant, while PA reversed these scopolamine-induced effects. PA significantly improved cholinergic system reactivity, as indicated by decreased acetylcholinesterase (AChE) activity, increased choline acetyltransferase (ChAT) activity, and elevated levels of acetylcholine (ACh) in the hippocampus and frontal cortex. PA also significantly ameliorated neuroinflammation and oxidative stress in mice. These results suggest that PA might exert a significant neuroprotective effect on cognitive impairment, driven in part by the modulation of cholinergic activity and neuroinflammation. Copyright © 2015 Elsevier GmbH. All rights reserved.

  14. Antiamnesic Effects of Walnuts Consumption on Scopolamine-Induced Memory Impairments in Rats

    PubMed Central

    Harandi, Shaahin; Golchin, Leila; Ansari, Mehdi; Moradi, Alireza; Shabani, Mohammad; Sheibani, Vahid

    2015-01-01

    Introduction: Alzheimer’s disease (AD) is an age-related neurodegenerative disease, which impairs memory and cognitive function. Walnuts are a dietary source of polyphenols, antioxidants and other compounds with health beneficial effects. These characteristic of walnuts make them perfect candidates for evaluation of their possible effects on neurodegenerative diseases. Therefore the present study was designed to investigate the effects of walnuts consumption (2%, 6% and 9% walnut diets) on memory enhancement and acetylcholinesterase (AChE) activity of brain in scopolamine-induced amnesic rats. Methods: Learning, memory and locomotor activity parameters were evaluated using Morris water maze (MWM), passive avoidance and rotarod tests. Results: Our results showed that consumption of walnuts at doses of 6% and 9% significantly restored the scopolamine-induced memory impairments in the MWM and passive avoidance tests. Moreover, the potential of walnuts to prevent scopolamine neurotoxicity was also reflected by the decreased AChE activity in the whole brain in comparison with the scopolamine group. Discussion: These results suggest that walnuts may be useful against memory impairment and it may exert these anti-amnesic activities via inhibition of AChE activity in the brain. It would be worthwhile to explore the potential of this nut and its active components in the management of the AD. PMID:27307953

  15. Amnesia of Inhibitory Avoidance by Scopolamine Is Overcome by Previous Openfield Exposure

    ERIC Educational Resources Information Center

    Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge A.; Jerusalinsky, Diana A.

    2014-01-01

    The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two…

  16. Blockade of the dorsal hippocampal dopamine D1 receptors inhibits the scopolamine-induced state-dependent learning in rats.

    PubMed

    Piri, M; Rostampour, M; Nasehi, M; Zarrindast, M R

    2013-11-12

    In the present study, we investigated the possible role of the dorsal hippocampal (CA1) dopamine D1 receptors on scopolamine-induced amnesia as well as scopolamine state-dependent memory in adult male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24h after training for their step-through latency. Results indicated that pre-training or pre-test intra-CA1 administration of scopolamine (1.5 and 3 μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. The pre-training scopolamine-induced amnesia (3 μg/rat) was reversed by the pre-test administration of scopolamine, indicating a state-dependent effect. Similarly, the pre-test administration of dopamine D1 receptor agonist, 1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SKF38393; 1, 2 and 4 μg/rat, intra-CA1), could significantly reverse the scopolamine-induced amnesia. Interestingly, administration of an ineffective dose of scopolamine (0.25 μg/rat, intra-CA1) before different doses of SKF38393, blocked the reversal effect of SKF38393 on the pre-training scopolamine-induced amnesia. Moreover, while the pre-test intra-CA1 injection of the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.1 and 0.5 μg/rat, intra-CA1), resulted in apparent memory impairment, microinjection of the same doses of this agent inhibited the scopolamine-induced state-dependent memory. These results indicate that the CA1 dopamine D1 receptors may potentially play an important role in scopolamine-induced amnesia as well as the scopolamine state-dependent memory. Furthermore, our results propose that dopamine D1 receptor agonist, SKF38393 reverses the scopolamine-induced amnesia via acetylcholine release and possibly through the activation of muscarinic

  17. Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

    PubMed Central

    Furey, Maura L; Khanna, Ashish; Hoffman, Elana M; Drevets, Wayne C

    2010-01-01

    Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 μg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery–Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group × block interaction (F=21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F=8.4, p=0.006). The treatment group × block interaction was also significant in males (F=3.8, p=0.043) and females (F=35.6, p<0.001) separately. A block × gender interaction (F=7.4, p=0.009) indicated that the response magnitude was larger in women. The treatment × block interaction was significant for the HAM-A across gender (F=12.0, p<0.001), and was significant for females (F=24.9, p<0.001) but not for males (F=1.3, p=0.30). When comparing the baseline block to study end, the block × gender interaction (F=12.6, p=0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men. PMID:20736989

  18. Scopolamine produces larger antidepressant and antianxiety effects in women than in men.

    PubMed

    Furey, Maura L; Khanna, Ashish; Hoffman, Elana M; Drevets, Wayne C

    2010-11-01

    Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 μg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group × block interaction (F=21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F=8.4, p=0.006). The treatment group × block interaction was also significant in males (F=3.8, p=0.043) and females (F=35.6, p<0.001) separately. A block × gender interaction (F=7.4, p=0.009) indicated that the response magnitude was larger in women. The treatment × block interaction was significant for the HAM-A across gender (F=12.0, p<0.001), and was significant for females (F=24.9, p<0.001) but not for males (F=1.3, p=0.30). When comparing the baseline block to study end, the block × gender interaction (F=12.6, p=0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.

  19. Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018).

    PubMed

    Han, Xiang-Yu; Liu, He; Liu, Chun-He; Wu, Bo; Chen, Lan-Fu; Zhong, Bo-Hua; Liu, Ke-Liang

    2005-04-15

    A practical diastereoselective synthetic method for 8018 enantiopure isomers is described. The intramolecular asymmetric epoxidation of mono-sulfonate 4 was applied for the execution of the synthesis of the key chiral building block for the first time. The isomers were obtained with 70-76% yields in 99-100% ee.

  20. In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD.

    PubMed

    Profita, Mirella; Riccobono, Loredana; Montalbano, Angela Marina; Bonanno, Anna; Ferraro, Maria; Albano, Giusy Daniela; Gerbino, Stefania; Casarosa, Paola; Pieper, Michael Paul; Gjomarkaj, Mark

    2012-03-01

    Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspases 3 and 8 activity and choline levels, in PBT-cells from COPD patients. We showed that: (1) apoptosis, mAChR M(3) and ChAT expression and the CD3+ and CD8+ ACh-binding are increased in PBT-cells from COPD patients when compared to C subjects, while CD4+/CD8+ ratio of ACh-binding to PBT cells was reduced in COPD; (2) choline levels are higher in serum and PBT-cells extracts from COPD patients than in S and C; (3) Tiotropium and HCh-3 reduced CD4+ and increased CD8+ apoptosis via caspases 3 and 8 activities and via IκB mediated mechanisms in COPD patients. This study suggests the involvement of non-neuronal components of cholinergic system in the regulation of PBT-cell apoptosis in COPD and demonstrates that Tiotropium regulates CD4+ and CD8+ PBT-cell apoptosis. It provides novel putative pharmacological targets for the resolution of systemic inflammation in COPD. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. Relative Bioavailability of Scopolamine Dosage Forms and Interaction with Dextroamphetamine

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Du, Brian; Vaksman, Zalman; Locke, James P.; Putcha, Lakshmi

    2007-01-01

    The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) and in combination with dextoamphetamine (DEX) to manage motion sickness symptoms during parabolic flights. The medications are dispensed as custom dosage forms as gelatin capsules. Anecdotal evidence of efficacy suggests that these formulations are unreliable and less efficacious for the treatment of motion sickness. We estimated bioavailability of four different oral formulations used by NASA for the treatment of motion sickness. Twelve healthy, non-smoking subjects between 21and 48 years of age received four treatments on separate days in a randomized fashion; the treatments were 0.8 mg SCOP alone as tablet, 0.8 mg SCOP alone in gel cap, 0.8 mg SCOP and 10 mg DEX as tablets, and 0.8 mg SCOP and 10 mg DEX in gel cap. After each treatment, blood, saliva, and urine samples were collected at scheduled time intervals for 24 h after dosing. Bioavailability and pharmacokinetic parameters were calculated and compared using ANOVA. After administration of SCOP tablets alone, maximum concentration (C(sub max)) and time for maximum concentration (t(sub max)) were 0.26 plus or minus 0.04 ng/mL and 0.71 plus or minus 0.02 h, respectively; volume of distribution, and clearance were 47.6 plus or minus 4.72 L/kg and 23.0 plus or minus 4.58 L/h/kg, respectively. SCOP t(sub max) after administration as gelcaps was significantly longer than that with tablets (1.04 h, p less than 0.05), but no significant differences in other pharmacokinetic parameters of SCOP were observed between the two dosage forms. When coadministered with DEX, the area underneath the concentration versus time curve (AUC) of SCOP was significantly reduced to 0.61 plus or minus 0.09 and 0.64 plus or minus 0.11 ng (raised dot) h/mL after administration as a tablet or gelcap formulation, respectively; SCOP C(sub max) was lower after coadministration with DEX, this difference, however, was not statistically significant. Delayed absorption with gelcaps

  2. Relative Bioavailability of Scopolamine Dosage Forms and Interaction with Dextroamphetamine

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Du, Brian; Vaksman, Zalman; Locke, James P.; Putcha, Lakshmi

    2007-01-01

    The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) and in combination with dextoamphetamine (DEX) to manage motion sickness symptoms during parabolic flights. The medications are dispensed as custom dosage forms as gelatin capsules. Anecdotal evidence of efficacy suggests that these formulations are unreliable and less efficacious for the treatment of motion sickness. We estimated bioavailability of four different oral formulations used by NASA for the treatment of motion sickness. Twelve healthy, non-smoking subjects between 21and 48 years of age received four treatments on separate days in a randomized fashion; the treatments were 0.8 mg SCOP alone as tablet, 0.8 mg SCOP alone in gel cap, 0.8 mg SCOP and 10 mg DEX as tablets, and 0.8 mg SCOP and 10 mg DEX in gel cap. After each treatment, blood, saliva, and urine samples were collected at scheduled time intervals for 24 h after dosing. Bioavailability and pharmacokinetic parameters were calculated and compared using ANOVA. After administration of SCOP tablets alone, maximum concentration (C(sub max)) and time for maximum concentration (t(sub max)) were 0.26 plus or minus 0.04 ng/mL and 0.71 plus or minus 0.02 h, respectively; volume of distribution, and clearance were 47.6 plus or minus 4.72 L/kg and 23.0 plus or minus 4.58 L/h/kg, respectively. SCOP t(sub max) after administration as gelcaps was significantly longer than that with tablets (1.04 h, p less than 0.05), but no significant differences in other pharmacokinetic parameters of SCOP were observed between the two dosage forms. When coadministered with DEX, the area underneath the concentration versus time curve (AUC) of SCOP was significantly reduced to 0.61 plus or minus 0.09 and 0.64 plus or minus 0.11 ng (raised dot) h/mL after administration as a tablet or gelcap formulation, respectively; SCOP C(sub max) was lower after coadministration with DEX, this difference, however, was not statistically significant. Delayed absorption with gelcaps

  3. Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory deficit in mice.

    PubMed

    Ishola, Ismail Ogunbayode; Adeyemi, Olufunmilayo Olaide; Agbaje, Esther Oluwatoyin; Tota, Santoshkumar; Shukla, Rakesh

    2013-01-01

    Roots of Combretum mucronatum Schumach. & Thonn. (Combretaceae) and Capparis thonningii Schum. (Capparaceae) are used in southwest Nigeria in the treatment of inflammatory disorders and mental illness. This study evaluated the antidementic effect of the methanol root extracts of C. mucronatum and C. thonningii on scopolamine (3 mg/kg, i.p.) induced memory impairment in mice. The effect of C. mucronatum and C. thonningii (50-200 mg/kg) administered orally for 3 days on memory impairments induced in mice by scopolamine was assessed in the passive avoidance and Morris water maze test and compared with that of tacrine (5 mg/kg, i.p.). The activities of acetylcholinesterase (AchE) and antioxidant enzymes were estimated in the brain after the completion of behavioral studies. C. mucronatum and C. thonningii root extracts (50-200 mg/kg) reversed scopolamine-induced memory deficit with significant (p < 0.05) increase in transfer latency in passive avoidance test. Similarly, the extracts (200 mg/kg) ameliorated memory deficit as a result of significant (p < 0.001) decrease in escape latency and path length in Morris water maze test. The increased AChE activity induced by scopolamine was significantly (p < 0.05) inhibited by C. mucronatum and C. thonningii (100 and 200 mg/kg) treatment which was similar to the effect of tacrine. Both extracts significantly (p < 0.05) attenuated scopolamine-induced increase in oxidative stress parameters as well as restoration of glutathione activity. C. mucronatum and C. thonningii extracts possess significant anticholinesterase, antioxidant and antidementic properties, which may be useful in the management of Alzheimer's disease.

  4. Aqueous extracts from asparagus stems prevent memory impairments in scopolamine-treated mice.

    PubMed

    Sui, Zifang; Qi, Ce; Huang, Yunxiang; Ma, Shufeng; Wang, Xinguo; Le, Guowei; Sun, Jin

    2017-03-09

    Aqueous extracts from Asparagus officinalis L. stems (AEAS) are rich in polysaccharides, gamma-amino butyric acid (GABA), and steroidal saponin. This study was designed to investigate the effects of AEAS on learning, memory, and acetylcholinesterase-related activity in a scopolamine-induced model of amnesia. Sixty ICR mice were randomly divided into 6 groups (n = 10) including the control group (CT), scopolamine group (SC), donepezil group (DON), low, medium, and high dose groups of AEAS (LS, MS, HS; 1.6 mL kg(-1), 8 mL kg(-1), 16 mL kg(-1)). The results showed that 8 mL kg(-1) of AEAS used in this study significantly reversed scopolamine-induced cognitive impairments in mice in the novel object recognition test (P < 0.05) and the Y-maze test (P < 0.05), and also improved the latency to escape in the Morris water maze test (P < 0.05). Moreover, it significantly increased acetylcholine and inhibited acetylcholinesterase activity in the hippocampus, which was directly related to the reduction in learning and memory impairments. It also reversed scopolamine-induced reduction in the hippocampal brain-derived neurotrophic factor (BDNF) and the cAMP response element-binding protein (CREB) mRNA expression. AEAS protected against scopolamine-induced memory deficits. In conclusion, AEAS protected learning and memory function in mice by enhancing the activity of the cholinergic nervous system, and increasing BDNF and CREB expression. This suggests that AEAS has the potential to prevent cognitive impairments in age-related diseases, such as Alzheimer's disease.

  5. Effect of Gingko biloba extract on scopolamine-induced apoptosis in the hippocampus of rats.

    PubMed

    Jahanshahi, M; Nickmahzar, E G; Babakordi, F

    2013-09-01

    Apoptosis, known as programmed cell death, plays a crucial role in normal development and tissue homeostasis. Apoptosis is also involved in neurodegenerative diseases such as Alzheimer's disease. Amnesia refers to the loss of memory and can also be a warning sign of neurodegenerative diseases. The antioxidant properties of Ginkgo biloba extract was known previously. Therefore, the aim of this study was to examine the effects of Ginkgo biloba extract on the rat's hippocampal apoptotic neurons number after Scopolamine based amnesia. Thirty-six adult male Wistar rats were used. Rats were randomly divided into control, sham, protective and treatment groups. The rats in the sham group received only scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received Ginkgo biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before/after scopolamine injection. Then 48 h after the last injection, the brains of rats were withdrawn and fixed with paraformaldehyde, and then, after histological processing, the slices were stained with the TUNEL kit for apoptotic neurons. Data were compared by the ANOVA Post Hoc Tukey test; P < 0.05 was considered significant. Our results showed that Scopolamine (in the sham group) increased significantly the number of apoptotic neurons in all areas of the hippocampus compared with the control. Whereas, Ginkgo biloba extract reduce the neuronal apoptosis in the hippocampus before and/or after encounter with scopolamine. We concluded that pretreatment and treatment injection of Ginkgo biloba extract can have a protective effect for neurons and it can limit apoptosis in all area of the hippocampus.

  6. Sesame indicum, a nutritional supplement, elicits antiamnesic effect via cholinergic pathway in scopolamine intoxicated mice.

    PubMed

    Chidambaram, Saravana Babu; Pandian, Anbarasi; Sekar, Sathiya; Haridass, Sumathy; Vijayan, Ranju; Thiyagarajan, Lakshmi Kantham; Ravindran, Jayasree; Balaji Raghavendran, Hanumantha Rao; Kamarul, Tunku

    2016-12-01

    Present study was undertaken to evaluate the antiamnesic effect of Sesamum indicum (S. indicum) seeds (standardized for sesamin, a lignan, content) in scopolamine, a muscarinic antagonist intoxicated mice. Male Swiss albino mice (18-22 g bw) were pretreated with methanolic extract of sesame seeds (MSSE) (100 and 200 mg/kg/day, p.o) for a period of 14 days. Scopolamine (0.3 mg/kg, i.p.) was injected on day 14, 45 ± 10 min after MSSE administration. Antiamnesic effect of MSSE was evaluated using step-down latency (SDL) on passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. To unravel the mechanism of action, we examined the effects of MSSE on the genes such as acetyl cholinesterase (AChE), muscarinic receptor M1 subtype (mAChRM1 ), and brain derived neurotrophic factor (BDNF) expression within hippocampus of experimental mice. Further, its effects on bax and bcl-2 were also evaluated. Histopathological examination of hippocampal CA1 region was performed using cresyl violet staining. MSSE treatment produced a significant and dose dependent increase in step down latency in passive avoidance test and decrease in transfer latency in elevated plus maze in scopolamine intoxicated injected mice. MSSE down-regulated AChE and mAChRM1 and up-regulated BDNF mRNA expression. Further, it significantly down-regulated the bax and caspase 3 and up-regulated bcl-2 expression in scopolamine intoxicated mice brains. Mice treated with MSSE showed increased neuronal counts in hippocampal CA1 region when compared with scopolamine-vehicle treated mice. Sesame seeds have the ability to interact with cholinergic components involved in memory function/restoration and also an interesting candidate to be considered for future cognitive research. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1955-1963, 2016. © 2015 Wiley Periodicals, Inc.

  7. Behavioral effects and drug vulnerability in rats exposed to Pfiesteria toxin.

    PubMed

    Duncan, Perry M; Parris, Brian; Schultz, Sarah; Jones, Jermaine; Gordon, Andrew; Dyer, Brian; Marshall, Harold

    2005-01-01

    Pfiesteria piscicida is a dinoflagellate which has a lethal effect on fish and also causes a syndrome of toxic effects in humans. Cognitive impairment is a prominent aspect of Pfiesteria's toxicity, and this neurocognitive effect resulting from toxin exposure has been demonstrated previously in a rat model. Four experiments are presented here, which replicate, confirm and extend some of the initial research and also show that similar cognitive deficits result from exposure to the toxin of another species, Pfiesteria shumwayae. Rats were given intraperitoneal injections of filtered water taken from toxic Pfiesteria cultures and tested in the radial arm maze (RAM). In two experiments, exposure to toxin from either species (piscicida or shumwayae) retarded acquisition of RAM performance in a non-interrupted win-shift RAM paradigm. A scopolamine challenge showed increased vulnerability to anticholinergic effects in exposed rats, even after nondrugged RAM performance was not different from controls. A third experiment featured a more difficult RAM test which included a 150-min interruption-delay. Toxin exposure also degraded performance in this version of the RAM, and the impairment was potentiated by the scopolamine challenge. The fourth experiment demonstrated retarded learning of the reversal of a RAM procedure which tested reference memory. In agreement with earlier research, these results indicate that Pfiesteria toxin interferes with the learning required to adapt to changing behavioral requirements. They also demonstrate that a latent toxin-produced CNS dysfunction persists after behavior appears normal, as revealed by potentiation of scopolamine's impairment of efficient RAM performance.

  8. Serotonergic or Anticholinergic Toxidrome: Case Report of a 9-Year-Old Girl.

    PubMed

    Gerardi, Diana M; Murphy, Tanya K; Toufexis, Megan; Hanks, Camille

    2015-12-01

    The aim of this study was to report an acute onset of symptoms erroneously attributed to serotonin syndrome in a child who had been given both anticholinergic and serotonergic agents. A 9-year-old girl with chronic anxiety and gastrointestinal problems was prescribed oral sertraline 6.25 mg daily, as well as hyoscyamine, ondansetron, montelukast, and a course of nitazoxanide. She was also routinely given diphenhydramine and omeprazole. Three days after increasing sertraline to 12.5 mg, she presented to the emergency department with altered mental status, hallucinations, mydriasis, tachycardia, and pyrexia. She was admitted to the pediatric intensive care unit and subsequently treated unsuccessfully for serotonin syndrome, with blurred vision and clonus persisting at discharge 4 days after admittance. Upon follow-up with her outpatient clinic, all anticholinergic agents were discontinued, and symptoms slowly resolved. This case illustrates the importance of differential diagnosis between toxidromes and how clinical presentation can be altered by preexisting conditions as well as the use of medications that affect multiple neurotransmitter systems.

  9. Impact of treatment of overactive bladder with anticholinergics on sexual function.

    PubMed

    Jha, Swati

    2016-02-01

    To establish if an improvement in OAB symptoms by treatment with anticholinergics is associated with a corresponding improvement in sexual function. This was a prospective observational questionnaire study using ePAQ-PF (electronic Pelvic Assessment Questionnaire-Pelvic Floor), PISQ 12 and PGI-I for overactive bladder and sexual function. Sexually active women with overactive bladder were included in the study. Prolapse and voiding dysfunction were exclusion criteria for the study. All women were followed up for 6 months and were treatment naïve. Sexual function before and after treatment was compared. The data were analysed using SPSS. Formal ethical approval was obtained. 34 women were included in the study. Only 8 % of women commenced on anticholinergics had an improvement in sexual function, compared to 66 % who experienced an improvement in OAB symptoms. Women who did experience a benefit in sexual function did so in the first 3 months of treatment of their overactive bladder and always noted an improvement in OAB symptoms. Treatment of the overactive bladder symptoms does not guarantee improvement in sexual function.

  10. Effect of physostigmine and gastric lavage in a Datura stramonium-induced anticholinergic poisoning epidemic.

    PubMed

    Salen, Philip; Shih, Richard; Sierzenski, Paul; Reed, James

    2003-07-01

    This study examines the impact of the administration of physostigmine and of nasogastric evacuation of Jimsonweed seeds on intensive-care unit (ICU) use and the length of stay in the hospital after Jimsonweed poisoning. Clinical data for this retrospective study were gathered from records of consecutive patients treated for Jimsonweed poisoning from September to November 1997. Descriptive statistics, Fisher's exact test, and Student t-test were used to analyze important clinical and sociodemographic variables. There were 17 victims of the Jimsonweed ingestion epidemic, all of whom presented with an anticholinergic toxidrome 3 to 9 hours after ingestion. Reported quantities of seed ingestion ranged from a low of 7 seeds to as high as 200 seeds. Altered mentation, manifested by combative behavior, necessitated admission of 13 patients to the ICU. The administration of physostigmine did not reduce admissions to the ICU (P = 0.54) or reduce length of stay in the hospital (P = 0.45) compared with the use of benzodiazepines alone. Nasogastric lavage was performed in 14 (82%) and seeds were recovered in 8 (57%) of those lavaged. The successful removal of Jimsonweed seeds did not decrease ICU use rates (P = 0.68) or shorten length of stay in the hospital compared with not recovering seeds (P = 0.85). The use of physostigmine and the successful nasogastric lavage of Jimsonweed seeds did not result in decreased intensive-care use or shorter length of stay in the hospital for Jimsonweed-induced anticholinergic toxicity.

  11. Transdermal drug delivery treatment for overactive bladder.

    PubMed

    Dmochowski, Roger R; Starkman, Jonathan S; Davila, G Willy

    2006-01-01

    Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and incontinence, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing side effects (e.g., dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin (N-DEO) is produced and this compound is deemed to be responsible for anticholinergic side effects such as dry mouth. This novel oxybutynin formulation offers patients with OAB and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.

  12. Comparison of reversal and adverse effects of sugammadex and combination of — Anticholinergic-Anticholinesterase agents in pediatric patients

    PubMed Central

    Özgün, Çiğdem; Çakan, Türkay; Baltacı, Bülent; Başar, Hülya

    2014-01-01

    Background: We aimed to compare clinical effects of sugammadex versus combination of anticholinergic-anticholinesterase agents for reversing of nondepolarizing neuromuscular block in pediatric patients. Materials and Methods: A total of 60 pediatric patients whom should be performed general anesthesia in the supine position were enrolled to this randomized double-blinded clinical trial. Fentanyl 1 μg/kg, propofol 2 mg/kg, rocuronium 0.6 mg/kg were used in induction and sevofluran, 50% O2-50% N2O in maintenance of anesthesia. Neuromuscular conductions were assessed by train of four (TOF)-Watch SX (Organon, Schering-Plough, Ireland) acceleromyograph. Patients were intubated at the moment of TOF 0. At the end of the operation emergence of T2 point was replied by 2 mg/kg sugammadex administration in group 1 and 0.06 mg/kg neostigmine +0.02 mg/kg atropine in group 2. At the moment of T0.9 inhalation, gases were ceased, and patients were extubated. Hemodynamic alterations, access to T0.9, extubation time, recovery parameters, drug consumptions and adverse effects were recorded. Results: Train of four scores showed a lesser increase in group 2 than group 1 from 15th s to 30th min during post reverse period (from 6.9 ± 6.4 to 91.7 ± 7.2 in group 2 vs. from 35.4 ± 21.4 to 99.5 ± 1.0 in group 1) (p < 0.0004). Group 1 patients exhibited much more complete muscle strength rates than group 2 (P < 0.001). T0.9 and extubation times were significantly longer in group 2 than group 1 (P < 0.001). Comparison of adverse effects yielded no difference. Conclusion: Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients. PMID:25422663

  13. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice.

    PubMed

    Giridharan, Vijayasree V; Thandavarayan, Rajarajan A; Sato, Shinji; Ko, Kam Ming; Konishi, Tetsuya

    2011-08-01

    The preventive effect of schisandrin B (Sch B), an antioxidant ingredient of Schisandra chinensis, was studied on scopolamine-induced dementia in mouse. Scopolamine developed oxidative stress in the brain with the decreased levels of antioxidant enzymes and increased nitrite level. At the same time, a significant impairment of learning and memory occurred when evaluated by passive avoidance task (PAT) and Morris water maze (MWM) with concomitant increase of acetylcholinesterase (AChE) activity and decreased acetylcholine levels. Pre-treatment by Sch B (10, 25, 50 mg/kg) effectively prevented scopolamine-induced oxidative stress and improved behavioural tasks. Further, the scopolamine-induced increase in AChE activity was significantly suppressed and the level of acetylcholine was maintained as normal by Sch B treatment. These results suggest that Sch B have protective function against cerebral functional defects such as dementia not only by antioxidant prevention but also exerting its potent cognitive-enhancing activity through modulation of acetylcholine level.

  14. 5-HT6 receptor antagonist reversal of emotional learning and prepulse inhibition deficits induced by apomorphine or scopolamine.

    PubMed

    Mitchell, Ellen S; Neumaier, John F

    2008-01-01

    5-HT6 receptors have been implicated in consolidation of visuospatial and reward-based learning tasks. Since 5-HT6 receptors may be important in modulation of sensory gating which is often affected in schizophrenic patients, we tested whether Ro 4368554, a 5-HT6 selective antagonist at a dose of 10 mg/kg, could reverse the loss of prepulse inhibition from apomorphine or scopolamine. In addition, we also tested whether Ro 4368554 altered fear conditioning using fear potentiated startle, a model for emotional learning. Prepulse inhibition of startle was disrupted by apomorphine (0.5 mg/kg) when prepulse emissions were 5 dB above background but not above 15 dB, while scopolamine (0.5 mg/kg) caused disruption at both prepulse levels. Scopolamine-mediated disruption was not reversed by Ro 4368854 but apomorphine-mediated disruption was significantly ameliorated by 5-HT6 inhibition. For fear potentiated startle, scopolamine and/or Ro 4368554 were administered before two daily fear conditioning sessions; rats were tested on the following day. Rats that received scopolamine displayed no fear potentiated startle but Ro 4368554 reversed this scopolamine deficit. Additionally, we mapped Fos induction in rats treated with scopolamine and/or Ro 4368554; scopolamine increased Fos expression in the central nucleus of the amygdala and this was attenuated by Ro 4368554. In summary, we have demonstrated the efficacy of 5-HT6 antagonists in modulating sensory gating and fear conditioning, and thus may be of therapeutic use for schizophrenia-related disorders.

  15. Paradoxical facilitation of object recognition memory after infusion of scopolamine into perirhinal cortex: implications for cholinergic system function.

    PubMed

    Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2006-09-13

    The cholinergic system has long been implicated in learning and memory, yet its specific function remains unclear. In the present study, we investigated the role of cortical acetylcholine in a rodent model of declarative memory by infusing the cholinergic muscarinic receptor antagonist scopolamine into the rat perirhinal cortex during different stages (encoding, storage/consolidation, and retrieval) of the spontaneous object recognition task. Presample infusions of scopolamine significantly impaired object recognition compared with performance of the same group of rats on saline trials; this result is consistent with previous reports supporting a role for perirhinal acetylcholine in object information acquisition. Scopolamine infusions directly before the retrieval stage had no discernible effect on object recognition. However, postsample infusions of scopolamine with sample-to-infusion delays of up to 20 h significantly facilitated performance relative to postsample saline infusion trials. Additional analysis suggested that the infusion episode could cause retroactive or proactive interference with the sample object trace and that scopolamine blocked the acquisition of this interfering information, thereby facilitating recognition memory. This is, to our knowledge, the first example of improved recognition memory after administration of scopolamine. The overall pattern of results is inconsistent with a direct role for cortical acetylcholine in declarative memory consolidation or retrieval. Rather, the cholinergic input to the perirhinal cortex may facilitate acquisition by enhancing the cortical processing of incoming stimulus information.

  16. Anti-amnesic activity of Citrus aurantium flowers extract against scopolamine-induced memory impairments in rats.

    PubMed

    Rahnama, Samira; Rabiei, Zahra; Alibabaei, Zahra; Mokhtari, Shiva; Rafieian-Kopaei, Mahmoud; Deris, Fatemeh

    2015-04-01

    Alzheimer's disease (AD) is a progressive neurological disorder that mostly affects the elderly population. Learning and memory impairment as the most characteristic manifestation of dementia could be induced chemically by scopolamine, a cholinergic antagonist. Cholinergic neurotransmission mediated brain oxidative stress. Citrus aurantium (CA) has traditionally been used for the treatment of insomnia, anxiety and epilepsy. The present study was designed to investigate the effect of Citrus aurantium on scopolamine-induced learning and memory deficit in rats. Forty-two Wistar rats were divided into six equal groups. (1) Control (received saline), (2) SCOP (scopolamine at a dose of 1 mg/kg for 15 days), (3) and (4) SCOP + CA (scopolamine and CA extract at doses of 300 and 600 mg/kg per day for 15 days), (5) and (6) intact groups (CA extract at 300 and 600 mg/kg per day for 15 days, respectively). Administration of CA flower extract significantly restored memory and learning impairments induced by scopolamine in the passive avoidance test and also reduced escape latency during trial sessions in the Morris water maze test. Citrus aurantium flower extract significantly decreased the serum malondialdehyde (MDA) levels. Citrus aurantium flower extract has repairing effects on memory and behavioral disorders produced by scopolamine and may have beneficial effects in the treatment of AD.

  17. Cognition Enhancing and Neuromodulatory Propensity of Bacopa monniera Extract Against Scopolamine Induced Cognitive Impairments in Rat Hippocampus.

    PubMed

    Pandareesh, M D; Anand, T; Khanum, Farhath

    2016-05-01

    Cognition-enhancing activity of Bacopa monniera extract (BME) was evaluated against scopolamine-induced amnesic rats by novel object recognition test (NOR), elevated plus maze (EPM) and Morris water maze (MWM) tests. Scopolamine (2 mg/kg body wt, i.p.) was used to induce amnesia in rats. Piracetam (200 mg/kg body wt, i.p.) was used as positive control. BME at three different dosages (i.e., 10, 20 and 40 mg/kg body wt.) improved the impairment induced by scopolamine by increasing the discrimination index of NOR and by decreasing the transfer latency of EPM and escape latency of MWM tests. Our results further elucidate that BME administration has normalized the neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptamine, dopamine, 3,4 dihydroxyphenylacetic acid, norepinephrine) levels that were altered by scopolamine administration in hippocampus of rat brain. BME administration also ameliorated scopolamine effect by down-regulating AChE and up-regulating BDNF, muscarinic M1 receptor and CREB expression in brain hippocampus confirms the potent neuroprotective role and these results are in corroboration with the earlier in vitro studies. BME administration showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant and lipid peroxidation. These results indicate that, cognition-enhancing and neuromodulatory propensity of BME is through modulating the expression of AChE, BDNF, MUS-1, CREB and also by altering the levels of neurotransmitters in hippocampus of rat brain.

  18. Antiamnesic and Antioxidants Effects of Ferulago angulata Essential Oil Against Scopolamine-Induced Memory Impairment in Laboratory Rats.

    PubMed

    Hritcu, Lucian; Bagci, Eyup; Aydin, Emel; Mihasan, Marius

    2015-09-01

    Ferulago angulata (Apiaceae) is a shrub indigenous to western Iran, Turkey and Iraq. In traditional medicine, F. angulata is recommended for treating digestive pains, hemorrhoids, snake bite, ulcers and as sedative. In the present study, the effects of inhaled F. angulata essential oil (1 and 3%, daily, for 21 days) on spatial memory performance were assessed in scopolamine-treated rats. Scopolamine-induced memory impairments were observed, as measured by the Y-maze and radial arm-maze tasks. Decreased activities of superoxide dismutase, glutathione peroxidase and catalase along with increase of acetylcholinesterase activity and decrease of total content of reduced glutathione were observed in the rat hippocampal homogenates of scopolamine-treated animals as compared with control. Production of protein carbonyl and malondialdehyde significantly increased in the rat hippocampal homogenates of scopolamine-treated animals as compared with control, as a consequence of impaired antioxidant enzymes activities. Additionally, in scopolamine-treated rats exposure to F. angulata essential oil significantly improved memory formation and decreased oxidative stress, suggesting memory-enhancing and antioxidant effects. Therefore, our results suggest that multiple exposures to F. angulata essential oil ameliorate scopolamine-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

  19. Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity.

    PubMed

    Hasegawa, Yasushi; Inoue, Tatsuro; Kawaminami, Satoshi; Fujita, Miho

    2016-07-01

    To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test. Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test. Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex. Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine. Scallop shell extract also suppressed the increase in locomotor activity induced by MK801. Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  20. Dorsolateral frontal cortex and peripheral muscarinic receptors participation in the discriminative stimulus properties of scopolamine in rats.

    PubMed

    Aguayo-DelCastillo, Alejandra; Vélazquez-Martínez, David N; Sánchez-Castillo, Hugo; Casasola, César

    2013-08-01

    Organisms are capable of making decisions based on their ability to discriminate between different stimuli. This principle is fundamental for the adaptation of organisms to their environment, by emitting appropriate behaviors based on a previously acquired discriminative process. The present study analyzed the participation of the peripheral nervous system, the M₁ muscarinic receptor subtype, as well as the contribution of the dorsolateral frontal cortex to discrimination process using scopolamine as discriminative stimulus. Male Wistar rats were trained to discriminate between scopolamine (1.0 mg/kg) and saline injections (i.p.) using a two-lever operant procedure. Once discrimination was acquired, generalization curves for scopolamine, methylscopolamine, pirenzepine, dorsolateral frontal cortex lesion and control conditions were obtained. Results showed that rats were able to discriminate and generalize its responses to different doses of scopolamine but not for methylscopolamine or pirenzepine, thus the data suggest that discriminative properties of scopolamine are processed in CNS and that the M₁ receptor does not participate in this process. Dorsolateral frontal cortex lesion did not produce any statistically significant difference in the generalization curve, which suggests that a system different from the dorsolateral prefrontal cortex may be responsible for the control of stimulus produced by scopolamine. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Melatonin attenuates scopolamine-induced memory/synaptic disorder by rescuing EPACs/miR-124/Egr1 pathway.

    PubMed

    Wang, Xiong; Wang, Zhi-Hao; Wu, Yuan-Yuan; Tang, Hui; Tan, Lu; Wang, Xiang; Gao, Xin-Ya; Xiong, Yan-Si; Liu, Dan; Wang, Jian-Zhi; Zhu, Ling-Qiang

    2013-02-01

    Alzheimer's disease (AD) is the most prevalent type of dementia in elderly people. There are decreased melatonin levels in the serum of AD patients, and melatonin supplements are able to reverse AD pathology and memory deficits in many animal experiments and clinical trials. However, the underlying mechanism regarding how melatonin rescues the AD-like memory/synaptic disorder remains unknown. Here, we use the Morris water maze, step-down inhibitory avoidance task, in vivo long-term potentiation recording, and Golgi staining and report that intraperitoneal injection of melatonin (1 mg/kg/day) for 14 days in rats effectively reverses the memory and synaptic impairment in scopolamine-induced amnesia, a well-recognized dementia animal model. Using real-time polymerase chain reaction and western blotting experiments, we further determined that melatonin rescues the EPACs/miR-124/Egr1 signal pathway, which is important in learning and memory, as reported recently. Our studies provide a novel underlying epigenetic mechanism for melatonin to attenuate the synaptic disorder and could benefit drug discovery in neurodegenerative diseases.

  2. Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice.

    PubMed

    Park, Hee Ra; Lee, Heeeun; Park, Hwayong; Cho, Won-Kyung; Ma, Jin Yeul

    2016-03-04

    We investigated the anti-amnesic effects of SJ and fermented SJ (FSJ) on scopolamine (SCO)-induced amnesia mouse model. Mice were orally co-treated with SJ or FSJ (125, 250, and 500 mg/kg) and SCO (1 mg/kg), which was injected intraperitoneally for 14 days. SCO decreased the step-through latency and prolonged latency time to find the hidden platform in the passive avoidance test and Morris water maze test, respectively, and both SCO effects were ameliorated by FSJ treatment. FSJ was discovered to promote hippocampal neurogenesis during SCO treatment by increasing proliferation and survival of BrdU-positive cells, immature/mature neurons. In the hippocampus of SCO, oxidative stress and the activity of acetylcholinesterase were elevated, whereas the levels of acetylcholine and choline acetyltransferase were diminished; however, all of these alterations were attenuated by FSJ-treatment. The alterations in brain-derived neurotrophic factor, phosphorylated cAMP response element-binding protein, and phosphorylated Akt that occurred following SCO treatment were protected by FSJ administration. Therefore, our findings are the first to suggest that FSJ may be a promising therapeutic drug for the treatment of amnesia and aging-related or neurodegenerative disease-related memory impairment. Furthermore, the molecular mechanism by which FSJ exerts its effects may involve modulation of the cholinergic system and BDNF/CREB/Akt pathway.

  3. Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice

    PubMed Central

    Park, Hee Ra; Lee, Heeeun; Park, Hwayong; Cho, Won-Kyung; Ma, Jin Yeul

    2016-01-01

    We investigated the anti-amnesic effects of SJ and fermented SJ (FSJ) on scopolamine (SCO)-induced amnesia mouse model. Mice were orally co-treated with SJ or FSJ (125, 250, and 500 mg/kg) and SCO (1 mg/kg), which was injected intraperitoneally for 14 days. SCO decreased the step-through latency and prolonged latency time to find the hidden platform in the passive avoidance test and Morris water maze test, respectively, and both SCO effects were ameliorated by FSJ treatment. FSJ was discovered to promote hippocampal neurogenesis during SCO treatment by increasing proliferation and survival of BrdU-positive cells, immature/mature neurons. In the hippocampus of SCO, oxidative stress and the activity of acetylcholinesterase were elevated, whereas the levels of acetylcholine and choline acetyltransferase were diminished; however, all of these alterations were attenuated by FSJ-treatment. The alterations in brain-derived neurotrophic factor, phosphorylated cAMP response element-binding protein, and phosphorylated Akt that occurred following SCO treatment were protected by FSJ administration. Therefore, our findings are the first to suggest that FSJ may be a promising therapeutic drug for the treatment of amnesia and aging-related or neurodegenerative disease-related memory impairment. Furthermore, the molecular mechanism by which FSJ exerts its effects may involve modulation of the cholinergic system and BDNF/CREB/Akt pathway. PMID:26939918

  4. Anticholinergic delirium following Datura stramonium ingestion: Implications for the Internet age.

    PubMed

    Vearrier, David; Greenberg, Michael I

    2010-07-01

    Recreational use of Datura to deliberately induce an anticholinergic delirium is not uncommon. We present a case of Datura intoxication in a young adult who learned about the recreational use of Datura on the Internet and subsequently purchased Datura stramonium seeds from an online vendor. Using the Google search engine, we conducted searches for "Datura," "jimson weed" and "Datura seeds" and reviewed the first 200 search results for each search term. We found 16 websites recommending the recreational use of Datura, 12 vendors selling seeds of genus Datura and one website that both promoted the recreational use of Datura and also sold Datura stramonium leaves. The promotion of recreational use of Datura on the Internet represents a danger to public health and the ability to purchase Datura seeds from Internet vendors may increase the prevalence of Datura abuse.

  5. Anticholinergic delirium following Datura stramonium ingestion: Implications for the Internet age

    PubMed Central

    Vearrier, David; Greenberg, Michael I

    2010-01-01

    Recreational use of Datura to deliberately induce an anticholinergic delirium is not uncommon. We present a case of Datura intoxication in a young adult who learned about the recreational use of Datura on the Internet and subsequently purchased Datura stramonium seeds from an online vendor. Using the Google search engine, we conducted searches for “Datura,” “jimson weed” and “Datura seeds” and reviewed the first 200 search results for each search term. We found 16 websites recommending the recreational use of Datura, 12 vendors selling seeds of genus Datura and one website that both promoted the recreational use of Datura and also sold Datura stramonium leaves. The promotion of recreational use of Datura on the Internet represents a danger to public health and the ability to purchase Datura seeds from Internet vendors may increase the prevalence of Datura abuse. PMID:20930988

  6. Ameliorative effect of betulin from Betula platyphylla bark on scopolamine-induced amnesic mice.

    PubMed

    Cho, Namki; Kim, Hyeon Woo; Lee, Hee Kyoung; Jeon, Byung Ju; Sung, Sang Hyun

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease induced by cholinergic neuron damage or amyloid-beta aggregation in the basal forebrain region and resulting in cognitive disorder. We previously reported on the neuroprotective effects of Betula platyphylla bark (BPB) in an amyloid-beta-induced amnesic mouse model. In this study, we obtained a cognitive-enhancing compound by assessing results using a scopolamine-induced amnesic mouse model. Our results show that oral treatment of mice with BPB and betulin significantly ameliorated scopolamine-induced memory deficits in both passive avoidance and Y-maze tests. In the Morris water maze test, administration of BPB and betulin significantly improved memory and cognitive function indicating the formation of working and reference memories in treated mice. Moreover, betulin significantly increased glutathione content in mouse hippocampus, and the increase was greater than that from betulinic acid treatment. We conclude that BPB and its active component betulin have potential as therapeutic, cognitive enhancer in AD.

  7. Differential Effect of an Anticholinergic Antidepressant on Sleep-Dependent Memory Consolidation

    PubMed Central

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-01-01

    Study Objectives: Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory – the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Design: Double-blind, placebo-controlled, randomized, parallel-group study. Setting: Sleep laboratory. Participants: Twenty-five healthy men (mean age: 26.8 ± 5.6 y). Interventions: 75 mg amitriptyline versus placebo. Measurements/Results: To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Conclusions: Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline. Citation: Goerke M, Cohrs S, Rodenbeck A, Kunz D. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation. SLEEP

  8. 'Bad guys' among the antiparkinsonian drugs.

    PubMed

    Pirtosek, Zvezdan

    2009-03-01

    The first effective drugs for Parkinson's disease (PD) were anticholinergics, introduced at the end of 19.th century by Charcot. Since the introduction of levodopa in the sixties of the previous century, many new drugs have emerged for the treatment of Parkinson's disease: dopamine agonists (ergot as well as non-ergot, bromocriptine, pergolide, mirapexine, ropinirole), MAO B inhibitors (selegiline, rasagiline), amantadine, COMT inhibitors (entacapone, tolcapone). In all stages of the disease, levodopa remains the most effective drug for improving motor symptoms in PD. However, long term treatment with levodopa is accompanied by the development of motor fluctuations, dyskinesia, cognitive and neuropsychiatric adverse effects and increasingly diverse spectrum of drugs is needed to alleviate motor and nonmotor symptoms. Some of these drugs have caused considerable concern and controversies and were regarded at certain points as the 'bad guys' of Parkinson's disease pharmacological armamentarium. In the article, a short review of 'bad guys' including anticholinergics, selegiline, tolcapone and dopamine agonists, is given.

  9. Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments.

    PubMed

    Mansouri, Mohammad Taghi; Farbood, Yaghoub; Naghizadeh, Bahareh; Shabani, Sohreh; Mirshekar, Mohammad Ali; Sarkaki, Alireza

    2016-10-01

    Context In a previous study, it has been shown that ellagic acid (EA), a polyphenolic compound found in pomegranate and different berries, prevents cognitive and hippocampal long-term potentiation (LTP) impairments induced by traumatic brain injury in rats through antioxidant and anti-inflammatory mechanisms. Objective The present study was conducted to assess the potential of EA as a memory enhancer. Materials and methods The elevated plus maze (EPM) and passive avoidance (PA) paradigm were used to evaluate learning and memory parameters. Three doses (10, 30 and 100 mg/kg, i.p.) of EA were administered to animals. Memory impairment was induced by scopolamine treatment (0.4 mg/kg, i.p.) and/or diazepam (1 mg/kg, i.p.). Acquisition trials were carried out 30 min after scopolamine treatment and retention trials were performed for 5 min 24 h after the acquisition trials. Results EA at doses 30 and 100 mg/kg significantly reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) in the EPM and PA tests in mice. Also, EA at doses 30 and 100 mg/kg significantly antagonized the amnesia induced by diazepam (1 mg/kg, i.p.) in EPM test in rats. Moreover, chronic administration of EA at dose 30 mg/kg ameliorated the memory deficit induced by diazepam (1 mg/kg, i.p.) in rats. Discussion and conclusion This study demonstrates that ellagic acid is effective in preventing scopolamine- and diazepam-induced cognitive impairments without altering the animals' locomotion. This suggests the potential of EA application as a useful memory restorative agent in the treatment of dementia seen in elderly persons.

  10. Cognition Enhancing Activity of Sulforaphane Against Scopolamine Induced Cognitive Impairment in Zebra Fish (Danio rerio).

    PubMed

    Rajesh, Venugopalan; Ilanthalir, Sakthivel

    2016-10-01

    Several epidemiological studies have shown that consumption of large quantities of vegetables especially cruciferous vegetables (Broccoli and Brussels sprouts) can protect against chronic diseases. Sulforaphane, an isothiocynate found in cruciferous vegetables has been demonstrated to have neuroprotective effects in several experimental paradigms. This study was undertaken to examine the effect of sulforaphane on cognitive impairment in zebra fish model using a novel method of fear conditioning. Initially, the normal behaviour of zebra fishes was studied in light-dark tank for 10 min daily for 10 days. Fishes were then divided into seven groups of twelve in each. Group I served as normal, group II served as fear conditioned control, group III and group IV were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated respectively. Group V served as scopolamine (400 µM/L) induced memory impairment fishes. Group VI and VII were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated scopolamine induced memory impairment groups respectively. In normal behavioural analysis, fishes preferred to stay in dark compartment. The average number of entries into the dark and time spent in dark were significantly more. Fishes in group II to VII were individually subjected to fear conditioning passive avoidance task and evaluated for learned task memory. It was observed that the average number of entries into dark and time spent in dark were significantly decreased. After exposure to respective treatment fishes in group III to VII were subjected to cognitive evaluation. There was no significant difference in cognition of group III and IV fishes exposed to sulforaphane and piracetam alone respectively. Fishes exposed to scopolamine showed a significant cognitive impairment. Sulforaphane exposure prior to scopolamine significantly retained the memory of learned task. These findings suggest that sulforaphane might be a promising therapeutic agent for cognitive enhancement in

  11. Effects of Transdermal Scopolamine on Auditory-Monitoring Performance and Event-Related Potentials.

    DTIC Science & Technology

    1992-12-21

    abilities of those it was meant to help. Scopolamine’s side effects include drowsiness , fatigue , slowing, difficulties in performing concurrent tasks...and Donchin (1983). All summary ERP measurements were scored by machine. Thirty-two signal averages were formed for each subject, corresponding to the...Wilson, G.F., Herning, R.I, Pickworth, W., & VanOrden, K.F. (1992). The OMPAT Level I Neurophysiological Performance Assessment Battery: NPPAB

  12. DADS Analogues Ameliorated the Cognitive Impairments of Alzheimer-Like Rat Model Induced by Scopolamine.

    PubMed

    Manral, Apra; Meena, Poonam; Saini, Vikas; Siraj, Fouzia; Shalini, Shruti; Tiwari, Manisha

    2016-10-01

    The development of agents that affect two or more relevant targets has drawn considerable attention in treatment of AD. Diallyl disulfide (DADS), an active principle of garlic, has been reported to prevent APP processing by amyloidogenic pathway. Recently, we have reported a new series of DADS derivatives and our findings revealed that compound 7k and 7l could provide good templates for developing new multifunctional agents for AD treatment. Thus, the present study was constructed to investigate the neuroprotective effect of DADS analogues (7k and 7l) against Aβ-induced neurotoxicity in SH-SY5Y human neuroblastoma cells and in ameliorating the cognition deficit induced by scopolamine in rat model. The results indicated that compound 7k and 7l significantly inhibited Aβ1-42-induced neuronal cell death by inhibiting ROS generation. Moreover, they prevented apoptosis, in response to ROS, by restoring normal Bax/Bcl-2 ratio. Furthermore, it was observed that scopolamine-induced memory impairment was coupled by alterations in neurotransmitters, acetylcholinesterase activity and oxidative stress markers. Histological analysis revealed severe damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Administration of compounds 7k and 7l at 5 mg/kg significantly reversed scopolamine-induced behavioural, biochemical, neurochemical and histological changes in a manner comparable to standard donepezil. Together the present findings and previous studies indicate that compounds 7k and 7l have neuroprotective and cognition-enhancing effects, which makes them a promising multi-target candidate for addressing the complex nature of AD.

  13. Clove oil reverses learning and memory deficits in scopolamine-treated mice.

    PubMed

    Halder, Sumita; Mehta, Ashish Krishan; Kar, Rajarshi; Mustafa, Mohammad; Mediratta, Pramod Kumari; Sharma, Krishna Kishore

    2011-05-01

    The present study was performed to examine the effect of Eugenia caryophyllata (Myrtaceae) on learning and memory, and also evaluate whether it can modulate oxidative stress in mice. Passive avoidance step-down task and elevated plus-maze were used to assess learning and memory in scopolamine-treated mice. Oxidative stress parameters were also assessed in brain samples by estimating the malondialdehyde (MDA) and reduced glutathione (GSH) levels at the end of the study. Scopolamine (0.3 mg/kg, i. p.) produced impairment of acquisition memory as evidenced by a decrease in step-down latency and an increase in transfer latency on day 1, and also impairment of retention of memory on day 2. Pretreatment with clove oil (0.05 mL/kg and 0.1 mL/kg) for 3 weeks significantly reversed the increase in acquisition latency and all the doses (0.025, 0.05, 0.1 mL/kg, i. p.) reversed the increase in retention latency induced by scopolamine (0.3 mg/kg, i. p.) in elevated plus-maze. However, 0.05 mL/kg clove oil attenuated memory deficits in the passive avoidance step-down task. Brain samples showed a significant decrease in MDA levels in the group treated with clove oil (0.05 and 0.025 mL/kg). GSH levels were also increased in clove oil-treated mice though the results were not significant. Thus, it can be concluded that clove oil can reverse the short-term and long-term memory deficits induced by scopolamine (0.3 mg/kg, i. p.) and this effect can, to some extent, be attributed to decreased oxidative stress. © Georg Thieme Verlag KG Stuttgart · New York.

  14. The context preexposure facilitation effect in mice: a dose-response analysis of pretraining scopolamine administration.

    PubMed

    Brown, Kevin L; Kennard, John A; Sherer, Daniel J; Comalli, David M; Woodruff-Pak, Diana S

    2011-11-20

    The context preexposure facilitation effect (CPFE) is an elaboration of contextual fear conditioning and refers to enhanced contextual conditioning resulting from preexposure to the context prior to a separate, brief context-shock episode. A version of the CPFE developed by Rudy and colleagues in rats has demonstrated greater sensitivity to pre-training hippocampal insult relative to standard contextual fear conditioning preparations. Our aim was to adapt the Rudy CPFE procedures to mice. In Experiment 1 we compared performance of young adult male C57BL6/J mice on two versions of the CPFE. One version - not previously used in mice - adapted methods established by Rudy and colleagues, and the other CPFE task replicated procedures previously established in this mouse strain by Gould and colleagues. In Experiment 2 we compared the effects of pre-training intraperitoneal administration of moderate levels of scopolamine or methylscopolamine on contextual conditioning between mice trained using the Rudy CPFE method and a separate group trained using standard contextual fear procedures. Scopolamine is a muscarinic cholinergic receptor antagonist that impairs hippocampal function. Robust freezing to the conditioning context was observed in mice trained using the Rudy CPFE method (Experiment 1), and greater scopolamine-induced impairments in contextual freezing were observed using this CPFE method relative to mice trained using standard contextual fear procedures (Experiment 2). These findings support use of the Rudy CPFE task as a behavioral assay for hippocampal function in mice.

  15. Cognitive-Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice

    PubMed Central

    Lee, Hyeon Yong; Weon, Jin Bae; Jung, Youn Sik; Kim, Nam Young; Kim, Myong Ki; Ma, Choong Je

    2016-01-01

    Aronia melanocarpa (A. melanocarpa) berries are a fruit with a marked antioxidant effect. The objective of this study was to confirm the effect of A. melanocarpa berries extract against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance test. Moreover, we determined a possible mechanism of the cognitive-enhancing effect involving AChE activity and BDNF and p-CREB expression in the hippocampus of mice. A. melanocarpa berries extract attenuated the learning and memory impairment induced by scopolamine in the Morris water maze (79.3 ± 0.8 s of 200 mg/kg and 64.4 ± 10.7 s of 400 mg/kg on day 4) and passive avoidance tests (46.0 ± 41.1 s of 200 mg/kg and 25.6 ± 18.7 s of 400 mg/kg). A. melanocarpa berries extract reduced the acetylcholinesterase level in the hippocampus of scopolamine-injected mice and increased BDNF and p-CREB expression in the hippocampus. The major compound, cyanidin-3-O-galactoside, also reversed memory impairment. These results showed that A. melanocarpa berries extract improved memory impairment by inhibiting AChE and increasing BDNF and p-CREB expression, and cyanidin-3-O-galactoside may be responsible for the effect of A. melanocarpa berries extract. PMID:27239211

  16. The cholinergic REM induction test with RS 86 after scopolamine pretreatment in healthy subjects.

    PubMed

    Riemann, D; Hohagen, F; Fleckenstein, P; Schredl, M; Berger, M

    1991-09-01

    A shortened latency of rapid eye movement (REM) sleep is one of the most stable biological abnormalities described in depressive patients. According to the reciprocal interaction model of non-REM and REM sleep regulation, REM sleep disinhibition at the beginning of the night in depression is a consequence of heightened central nervous system cholinergic transmitter activity in relation to aminergic transmitter activity. A recent study has indicated that muscarinic supersensitivity, rather than quantitatively enhanced cholinergic activity, may be the primary cause of REM sleep abnormalities in depression. The present study tested this hypothesis by treating healthy volunteers for 3 days with a cholinergic antagonist (scopolamine) in the morning, in an effort to induce muscarinic receptor supersensitivity. On the last day of scopolamine administration, RS 86, an orally active cholinergic agonist, was administered before bedtime to test whether this procedure would induce sleep onset REM periods. Whereas scopolamine treatment tended to advance REM sleep and to heighten REM density in healthy controls in comparison to NaCl administration, the additional cholinergic stimulation did not provoke further REM sleep disinhibition. This result underlines the need to take a hypofunction of aminergic transmitter systems into account in attempts to explain the pronounced advance of REM sleep typically seen in depressives.

  17. Cholinergic modulation of pavlovian fear conditioning: effects of intrahippocampal scopolamine infusion.

    PubMed

    Gale, G D; Anagnostaras, S G; Fanselow, M S

    2001-01-01

    Cholinergic neurotransmission has been implicated in the acquisition of a variety of tasks, including Pavlovian fear conditioning. To more precisely define the role of cholinergic modulation in this process, the effect of site-specific cholinergic antagonism was assessed. Male Long-Evans rats were implanted with chronic, bilateral cannulae aimed at the dorsal hippocampus. Infusions of scopolamine hydrobromide (50 microg bilaterally) or phosphate-buffered saline (PBS) were made immediately prior to a signaled Pavlovian fear conditioning procedure. On consecutive days following training, all rats were given independent tests assessing freezing to both the training context and the tone conditional stimulus (CS). Relative to PBS infused controls, rats that received intrahippocampal infusions of scopolamine showed a significant attenuation of contextual freezing but comparable levels of freezing to the tone CS. Neither shock sensitivity nor general activity levels differed between rats infused with scopolamine or PBS. These findings suggest that fear conditioning to context, but not discrete CS, requires intact cholinergic neurotransmission in the hippocampus.

  18. Effects of scopolamine on a novel choice serial reaction time task.

    PubMed

    Higgs, S; Deacon, R M; Rawlins, J N

    2000-05-01

    Rats were trained on a novel attentional task adapted from the five-choice serial reaction time test first developed by Carli et al. [1983; Behav. Brain. Res., 9, 361-80]. The novel task required rats to detect the occurrence of brief light flashes in one of two spatial locations following trial initiation by a lever press. Blank trials were interleaved with stimulus trials and the rat had to make a different response to indicate the absence of a light. Occasional light-alone trials were also presented in which the visual stimulus appeared without forewarning. Pre-exposure to food for 60 min prior to test increased response omissions for all trials and slowed correct response latency, but failed to significantly alter accuracy. A decrease in light-stimulus duration (1-0.4 s) decreased accuracy, increased the reporting of blank trials and the number of light-alone trial omissions. Scopolamine (0.03-0.1 mg/kg) and scopolamine methylbromide (0.1 mg/kg) failed to affect accuracy, but increased light-alone trial omissions and lengthened correct response latency. The results confirm that the novel task is able to distinguish between motivational and attentional manipulations, and imply that scopolamine affected performance via nonattentional mechanisms.

  19. Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma.

    PubMed

    Kirkland, Scott W; Vandenberghe, Christine; Voaklander, Britt; Nikel, Taylor; Campbell, Sandra; Rowe, Brian H

    2017-01-11

    Inhaled short-acting anticholinergics (SAAC) and short-acting beta₂-agonists (SABA) are effective therapies for adult patients with acute asthma who present to the emergency department (ED). It is unclear, however, whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone. To conduct an up-to-date systematic search and meta-analysis on the effectiveness of combined inhaled therapy (SAAC + SABA agents) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma. We searched MEDLINE, Embase, CINAHL, SCOPUS, LILACS, ProQuest Dissertations & Theses Global and evidence-based medicine (EBM) databases using controlled vocabulary, natural language terms, and a variety of specific and general terms for inhaled SAAC and SABA drugs. The search spanned from 1946 to July 2015. The Cochrane Airways Group provided search results from the Cochrane Airways Group Register of Trials which was most recently conducted in July 2016. An extensive search of the grey literature was completed to identify any other potentially relevant studies. Included studies were randomised or controlled clinical trials comparing the effectiveness of combined inhaled therapy (SAAC and SABA) to SABA treatment alone to prevent hospitalisations in adults with acute asthma in the emergency department. Two independent review authors assessed studies for inclusion using pre-determined criteria. For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model and reporting heterogeneity (I²). For continuous outcomes, we reported individual trial results using mean differences (MD) and pooled results as weighted mean differences (WMD) or standardised mean differences (SMD) with 95% CIs using a random-effects model. We included 23 studies that involved a total of 2724

  20. Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

    PubMed

    Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A

    2013-08-01

    Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

  1. Determination of tropane alkaloids atropine and scopolamine by liquid chromatography-mass spectrometry in plant organs of Datura species.

    PubMed

    Jakabová, Silvia; Vincze, Lajos; Farkas, Agnes; Kilár, Ferenc; Boros, Borbála; Felinger, Attila

    2012-04-06

    Hyoscyamine (atropine) and scopolamine are the predominant tropane alkaloids in the Datura genus, occurring in all plant organs. The assessment of the alkaloid content of various plant parts is essential from the viewpoint of medical use, but also as a potential risk of toxicity for humans and animals. Therefore, a reliable method for the determination of tropane alkaloid content is of high importance. The present work aimed at the elaboration of a rapid method for determination of the most abundant Datura alkaloids by LC-MS technique using a new generation of core-shell particle packed column. Tropane alkaloid content was investigated in various plant organs of four Datura taxa (D. innoxia, D. metel, D. stramonium, and D. stramonium var. tatula), grown under the same conditions, in two developmental stages. We have developed a rapid LC-MS method for the quantitative determination of atropine and scopolamine, which was successfully applied to quantify the alkaloids in different plant organs (leaves, flowers, stems, seeds) of thorn apples after a simple sample preparation step. Elaboration and validation of the method and analysis of plant extracts were done by UFLC-MS technique, employing an Ascentis Express C18 column. Detection was done in positive ionization mode (ESI+) and the method suitability was evaluated by several validation characteristics. Quantitation limits are 333 and 167 pgmL(-1) for scopolamine and atropine, respectively, and the method shows very good repeatability. The analysis of Datura extracts revealed significant differences depending on the species, the organ and the sampling period. Atropine was found to be dominant over scopolamine in three out of the four taxa investigated. D. innoxia showed the highest concentrations of scopolamine in all organs examined, whereas D. metel accumulated the lowest scopolamine levels. Hyoscyamine, measured as atropine, was the highest in D. stramonium var. tatula, and the lowest in D. innoxia. Samples

  2. Anti-inflammatory and protective effects of MT-031, a novel multitarget MAO-A and AChE/BuChE inhibitor in scopolamine mouse model and inflammatory cells.

    PubMed

    Liu, Wei; Rabinovich, Alon; Nash, Yuval; Frenkel, Dan; Wang, Yuqiang; Youdim, Moussa B H; Weinreb, Orly

    2017-02-01

    Previous study demonstrated that the novel multitarget compound, MT-031 preserved in one molecule entity the beneficial properties of its parent drugs, rasagiline and rivastigmine, and exerted high dual potencies of monoamine oxidase-A (MAO-A) and cholinesterase (ChE) inhibition in acute-treated mice and neuroprotective effects against H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. The present study aimed to further investigate the anti-inflammatory and protective effects of MT-031 in scopolamine mouse model and inflammatory cell cultures. Our findings demonstrated that once daily chronic administration of MT-031 (5-10 mg/kg) to mice antagonized scopolamine-induced memory and cognitive impairments, displayed brain selective MAO-A and AChE/BuChE inhibition, increased the levels of striatal dopamine (DA), serotonin (5-HT) and norepinephrine and prevented the metabolism of DA and 5-HT. In addition, MT-031 upregulated mRNA expression levels of Bcl-2, the neurotrophic factors, (e.g., brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF)), the antioxidant enzyme catalase and the anti-inflammatory cytokine, neurotrophic tyrosine kinase receptor (Ntrk), and down-regulated the mRNA expression levels of the pro-inflammatory interleukin (IL)-6 in scopolamine-induced mice. In accordance, MT-031 was shown to reduce reactive oxygen species accumulation, increase the levels of anti-inflammatory cytokines, IL-10 and decrease the levels of the pro-inflammatory cytokines, IL-1β, IL-6, IL-17 and interferon-gamma (IFN-γ) in activated mouse splenocytes and microglial cells. Taken together, these pharmacological properties of MT-031 can be of clinical importance for developing this novel multitarget compound as a novel drug candidate for the treatment of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Phytochemical analysis, molecular docking and antiamnesic effects of methanolic extract of Silybum marianum (L.) Gaertn seeds in scopolamine induced memory impairment in mice.

    PubMed

    Nazir, Nausheen; Karim, Nasiara; Abdel-Halim, Heba; Khan, Imran; Wadood, Syed Fazal; Nisar, Muhammad

    2017-08-24

    Silybum marianum (L.) Gaertn and its main component silymarin have been extensively studied and have been found effective in various neurological disorders. The aim of the current study is to identify phytoconstituents in the methanolic extract (Me. Ext) of Silybum marianum (L.) Gaertn seeds and to study in-vivo the anti-amnesic effects along with in vitro antioxidant and acetylcholinesterase (AChE) and buteryl cholinesterase (BChE) inhibition potential. Induced fir docking (IFD) results have confirmed that quercetin, morin and rutin showed good affinity when docked into AChE binding site. The present study investigates the in-vitro AChE and BChE inhibition potential of the Me-Ext of Silybum marianum (L.) Gaertn at various concentrations (31.25, 62.50, 125, 250, 500, 1000µg/mL) using Ellman's spectrophotometric analysis, while antioxidant potential against DPPH and ABTS were determined using Brand-Williams spectrophotometric method. Furthermore, the in-vivo anti-amnesic effects of Me. Ext at the dose level of 50, 100 and 200mg/kg were also evaluated using scopolamine -induced memory impairment in mice in the novel object recognition test (NORT) and Y-maze test. The Me. Ext showed a concentration dependent inhibition of AChE and BChE with IC50 values of 110 and 130µg/mL respectively and antioxidant activity against DPPH and ABTS with IC50 values 280 and 220µg/mL, respectively. In mice, Me. Ext reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task (p< 0.05 versus scopolamine) and increase in the discrimination index in the NORT comparable to the standard drug donepezil 2mg/kg. HPLC-UV analysis showed the presence of quercetin, rutin and morin. Induced fit docking (IFD) was performed using quercetin, rutin and morin, Glide Gscore and IFD score of all compounds were consistent with their experimental AChE inhibitory activities. The results indicate that Silybum marianum (L

  4. Double blind placebo controlled trial of short term transdermal scopolamine on heart rate variability in patients with chronic heart failure.

    PubMed Central

    Venkatesh, G.; Fallen, E. L.; Kamath, M. V.; Connolly, S.; Yusuf, S.

    1996-01-01

    OBJECTIVE: To test the hypothesis that short term application of transdermal scopolamine increases heart rate variability (HRV) and restores sympathovagal balance in patients with stable congestive heart failure (CHF). DESIGN: A double blind placebo controlled crossover study. SETTING: Tertiary referral centre. PATIENTS: Twelve patients (mean age 66 (10)) with New York Heart Association class II-IV CHF. All patients had coronary artery disease (mean left ventricular ejection fraction 26.7 (8.9) %). INTERVENTION: Patients were randomly assigned to receive either a placebo skin patch or a transdermal scopolamine patch (Transderm, 0.05 mg/h). Patches remained in place for 48 hours with a 24 hour washout period before crossover. OUTCOME MEASURES: HRV was derived from (a) 24 hour time domain indices (mean RR interval, standard deviation of interbeat interval, and the baseline width of the frequency distribution of RR intervals) and (b) short data set (2.2 mm) power spectral measurements using autoregressive modelling. Autospectral measures were performed in both resting supine and standing (orthostatic) states. The 24 hour Holter record was obtained during the second day of patch application. RESULTS: There was a small but significant (P < 0.05) increase in all time domain HRV variables with scopolamine. There was a paradoxical fall in low frequency (LF) spectral power induced by orthostasis during baseline (-30%) and placebo (-34%) states. Conversely, scopolamine was associated with a 14% increase in LF power during orthostatic stress. Scopolamine thus significantly reduced the orthostatic fall in LF (P < 0.01) compared with either baseline or placebo values. No difference in circadian rhythm was seen between the scopolamine and placebo treatment periods. However, the abrupt fall in the high frequency (vagal) power during the early morning sleep-wake hours was reduced by scopolamine. Scopolamine was also associated with a significant rightward shift in the resting LF

  5. Comparative Effectiveness of Anticholinergic Therapy for Overactive Bladder in Women: A Systematic Review and Meta-analysis.

    PubMed

    Reynolds, W Stuart; McPheeters, Melissa; Blume, Jeffery; Surawicz, Tanya; Worley, Katherine; Wang, Li; Hartmann, Katherine

    2015-06-01

    To summarize evidence about reduction in voiding and resolution of urine loss in overactive bladder comparing data from the active drug arms with the placebo arms of randomized trials. We searched MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and ClinicalTrials.gov in March 2014. Multiple reviewers screened original research published in English on community-dwelling women with nonneurogenic overactive bladder undergoing pharmacotherapy with medications available in the United States. Studies in which women comprised less than 75% of the population or those with a sample size less than 50 were excluded. Study designs included randomized controlled trials for meta-analysis and cohorts, case-control, and case series for harms data. Our search identified 50 randomized controlled trials from among 144 candidate publications (one was of good quality, 38 fair, and 11 poor). Multiple team members performed data extraction independently with secondary review of data entry to ensure quality and validity. Studies were assessed for risk of bias. Meta-analysis was performed using fixed-effects regression models. The primary outcomes and measurements were the numbers of daily voids and urge incontinence episodes. Medications delivered as a daily dose reduced urge incontinence by 1.73 episodes per day (95% confidence interval [CI] 1.37-2.09) and voids by 2.06 per day (95% CI 1.66-2.46) from 2.79 (95% CI 0.70-4.88) and 11.28 (95% CI 7.77-14.80) at baseline, respectively. Placebo reduced urge incontinence episodes by 1.06 (95% CI 0.7-1.42) and voids by 1.2 (95% CI 0.72-1.67) per day. No individual agent demonstrated superiority over another. The majority (98%) of studies reporting funding were sponsored by industry. Evidence from more than 27,000 women participating in randomized controlled trials suggests that improvement in symptoms with anticholinergic management of overactive bladder is modest and rarely fully resolves symptoms.

  6. Cognitive enhancing effect of the fermented Gumiganghwal-tang on scopolamine-induced memory impairment in mice.

    PubMed

    Weon, Jin Bae; Lee, Jiwoo; Eom, Min Rye; Jung, Youn Sik; Ma, Choong Je

    2016-01-01

    Gumiganghwal-tang (GT) is a traditional herbal medicine that is widely used for its anti-inflammatory, analgesic, and antipyretic actions. Fermented GT has been reported to inhibit acetylcholinesterase (AChE) activity and to exert a neuroprotective effect. In this study, we investigated the effect of fermented GT against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance tests. The results of the Morris water maze test indicated that fermented GT significantly decreased escape latency, as compared with that observed in the scopolamine-treated group. In the prove test, fermented GT attenuated the decreased time spent in the target quadrant observed after scopolamine treatment. The results of the passive avoidance test indicated that the treatment with fermented GT increased latency time when compared with the scopolamine-treated group. Moreover, fermented GT inhibited AChE activity in the hippocampi of the treated mice. These results suggest that fermented GT reduced scopolamine-induced amnesia in mice through AChE inhibition. Therefore, we hypothesize that fermented GT may be a useful therapeutic agent for the prevention or treatment of neurodegenerative diseases.

  7. Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics: a post hoc analysis of the TIOSPIR trial

    PubMed Central

    Wise, Robert; Calverley, Peter MA; Dahl, Ronald; Dusser, Daniel; Metzdorf, Norbert; Müller, Achim; Fowler, Andy; Anzueto, Antonio

    2015-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. Aims: The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg. Methods: A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. Results: Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. Conclusions: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy. PMID:26540491

  8. Synthesis of various geometric and enantiomeric oxime O-(alpha- and beta-methylcholinyl) ethers as potential anticholinergic agents.

    PubMed

    Huerta, P L; Isaacson, E I; Brown, R G; Delgado, J N

    1977-08-01

    Various enantiomeric and geometric oxime O-(alpha- and beta-methylcholinyl) ethers were synthesized as potential anticholinergic agents. The synthesis, separation, resolution, and structural characterization of these compounds are reported. The first step of the synthetic pathway involved an oxime formation, with subsequent O-alkylation of the respective oxime with 2-chloro-N,N-dimethylpropylamine hydrochloride. The separation of the alpha- and beta-structural isomers utilized vacuum fractional distillation and/or column chromatography, and the resolution of the enantiomers was accomplished via the formation of tartrate diastereoisomers. A preliminary pharmacological evaluation for anticholinergic activity was conducted using a rat ileum assay. Structure-activity relationships, including some stereochemical properties and antimuscarinic activity, are discussed.

  9. Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics.

    PubMed

    Cho, Kang Jun; Kim, Hyo Sin; Koh, Jun Sung; Kim, Joon Chul

    2013-02-01

    The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E(2) (PGE(2)) in women with overactive bladder (OAB) following anticholinergic treatment. A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE(2) levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared. Urinary NGF and PGE(2) levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE(2) levels were not significantly different between pre- and post-treatment in either group. NGF and PGE(2) have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.

  10. Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats.

    PubMed

    Utkan, Tijen; Gocmez, Semil S; Regunathan, Soundararajan; Aricioglu, Feyza

    2012-10-01

    Agmatine (l-amino-4-guanidino-butane), a metabolite of L-arginine through the action of arginine decarboxylase, is a novel neurotransmitter. In the present study, effects of agmatine on cognitive functions have been evaluated by using one trial step-down passive avoidance and three panel runway task. Agmatine (20, 40, 80 mg/kg i.p.) was administered either in the presence or absence of a cholinergic antagonist, scopolamine (1 mg/kg i.p.). Scopolamine significantly impaired learning and memory in both passive avoidance and three panel runway test. Agmatine did not affect emotional learning, working and reference memory but significantly improved scopolamine-induced impairment of learning and memory in a dose dependent manner. Our results indicate that agmatine, as an endogenous substance, may have an important role in modulation of learning and memory functions.

  11. Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics.

    PubMed

    Schmid, D M; Sauermann, P; Werner, M; Schuessler, B; Blick, N; Muentener, M; Strebel, R T; Perucchini, D; Scheiner, D; Schaer, G; John, H; Reitz, A; Hauri, D; Schurch, B

    2006-07-01

    In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8

  12. Promoting scopolamine biosynthesis in transgenic Atropa belladonna plants with pmt and h6h overexpression under field conditions.

    PubMed

    Xia, Ke; Liu, Xiaoqiang; Zhang, Qiaozhuo; Qiang, Wei; Guo, Jianjun; Lan, Xiaozhong; Chen, Min; Liao, Zhihua

    2016-09-01

    Atropa belladonna is one of the most important plant sources for producing pharmaceutical tropane alkaloids (TAs). T1 progeny of transgenic A. belladonna, in which putrescine N-methyltransferase (EC. 2.1.1.53) from Nicotiana tabacum (NtPMT) and hyoscyamine 6β-hydroxylase (EC. 1.14.11.14) from Hyoscyamus niger (HnH6H) were overexpressed, were established to investigate TA biosynthesis and distribution in ripe fruits, leaves, stems, primary roots and secondary roots under field conditions. Both NtPMT and HnH6H were detected at the transcriptional level in transgenic plants, whereas they were not detected in wild-type plants. The transgenes did not influence the root-specific expression patterns of endogenous TA biosynthetic genes in A. belladonna. All four endogenous TA biosynthetic genes (AbPMT, AbTRI, AbCYP80F1 and AbH6H) had the highest/exclusive expression levels in secondary roots, suggesting that TAs were mainly synthesized in secondary roots. T1 progeny of transgenic A. belladonna showed an impressive scopolamine-rich chemotype that greatly improved the pharmaceutical value of A. belladonna. The higher efficiency of hyoscyamine conversion was found in aerial than in underground parts. In aerial parts of transgenic plants, hyoscyamine was totally converted to downstream alkaloids, especially scopolamine. Hyoscyamine, anisodamine and scopolamine were detected in underground parts, but scopolamine and anisodamine were more abundant than hyoscyamine. The exclusively higher levels of anisodamine in roots suggested that it might be difficult for its translocation from root to aerial organs. T1 progeny of transgenic A. belladonna, which produces scopolamine at very high levels (2.94-5.13 mg g(-1)) in field conditions, can provide more valuable plant materials for scopolamine production.

  13. Validation and scopolamine-reversal of latent learning in the water maze utilizing a revised direct platform placement procedure.

    PubMed

    Malin, David H; Schaar, Krystal L; Izygon, Jonathan J; Nghiem, Duyen M; Jabitta, Sikirat Y; Henceroth, Mallori M; Chang, Yu-Hsuan; Daggett, Jenny M; Ward, Christopher P

    2015-08-01

    The Morris water maze is routinely used to explore neurobiological mechanisms of working memory. Humans can often acquire working memory relevant to performing a task by mere sensory observation, without having to actually perform the task followed by reinforcement. This can be modeled in the water maze through direct placement of a rat on the escape platform so that it can observe the location, and then assessing the subject's performance in swimming back to the platform. However, direct placement procedures have hardly been studied for two decades, reflecting a controversy about whether direct placement resulted in sufficiently rapid and direct swims back to the platform. In the present study, utilizing revised training methods, a more comprehensive measure of trajectory directness, a more rigorous sham-trained control procedure and an optimal placement-test interval, rats swam almost directly back to the platform in under 4s, significantly more quickly and directly than sham-trained subjects. Muscarinic cholinergic mechanisms, which are inactivated by scopolamine, are essential to memory for standard learning paradigms in the water maze. This experiment determined whether this would also be true for latent learning. ANOVA revealed significant negative effects of scopolamine on both speed and accuracy of trajectory, as well as significant positive effects of direct placement training vs. sham-training. In a probe trial, placement-trained animals without scopolamine spent significantly more time and path length in the target quadrant than trained rats with scopolamine and sham-trained rats without scopolamine. Scopolamine impairments are likely due to effects on memory, since the same dose had little effect on performance with a visible platform. The revised direct placement model offers a means of further comparing the neural mechanisms of latent learning with those of standard instrumental learning.

  14. The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder

    PubMed Central

    Konac, Ece; Ure, Iyimser; Senol, Cem; Onen, Ilke Hacer; Sozen, Sinan; Menevse, Adnan

    2015-01-01

    Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children. PMID:26166934

  15. Acute versus subchronic pyridostigmine administration: Effects on the anticholinergic properties of atropine

    SciTech Connect

    Matthew, C.B.; Glenn, J.F.; Bowers, W.D.

    1993-05-13

    Acute, subchronic and chronic exposures to cholinergic compounds may result in differing effects. The efficacy of pyridostigmine bromide (PY) prophylaxis against organophosphorus poisoning depends on post exposure atropine (AT) administration. AT induces a dose-dependent increase in rate of rise of core temperature in heat exposed humans and rats. To determine whether AT's anticholinergic potency is altered following PY administration, we examined AT's effects following acute or subchronic (2 weeks) PY administration in the sedentary heat-stressed rat. Unrestrained rats were used in the following 8 groups of 12: acute (a,2 injections via tail vein) aSAL+SAL, aSAL+AT, aPY+SAL, aPY+AT; subchronic (c, osmotic pump + tail vein) cSAL+SAL, cSAL+AT, cPY+SAL, cPY+AT (SAL- saline, AT- 200 ug/kg, aPY- 100 ug/kg, cPY- 20 ug/hr.) Fifteen minutes following the final injection, rats were subjected to an ambient temperature of 41.5 deg C until a core temperature of 42.6 deg C was attained.

  16. Effects of discontinuation of long-term anticholinergic treatment in elderly schizophrenia patients.

    PubMed

    Drimer, T; Shahal, B; Barak, Y

    2004-01-01

    Anticholinergic medication (ACM) is frequently used in psychiatry to treat the side-effects of D2 blocking agents. However, ACM is not without adverse effects and, in the elderly, cognitive and memory impairments have been emphasized. The aim of this study was to evaluate the effects of discontinuation of ACM on cognitive functions in a group of elderly chronic schizophrenia patients. Twenty-seven elderly patients (age 60 years or older), who were diagnosed as suffering from schizophrenia (DSM-IV) and receiving ACM in addition to antipsychotic treatment, were enrolled. Before and after ACM was discontinued, the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale was administered. Twenty-one patients completed the study. All were receiving Akineton (biperiden), 2-6 mg daily before the study. Significant improvement in the ADAS-Cog total score was demonstrated (P < 0.03), as well as in the ideational praxia and orientation subscales. Improvement was correlated with the previous dose of biperidin. No adverse events or emergent extrapyramidal symptoms were noted. Discontinuation of ACM may be warranted in chronic schizophrenia patients since it may improve cognitive functioning with no adverse effects.

  17. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

    PubMed

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-05-01

    Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

  18. [Efficacy of glycopyrronium bromide and scopolamine hydrobromide in patients with death rattle: a randomized controlled study].

    PubMed

    Likar, Rudolf; Rupacher, Ernst; Kager, Hans; Molnar, Mario; Pipam, Wofgang; Sittl, Reinhard

    2008-01-01

    Death rattle is an extremely distressing symptom for the dying patient and for his environment. The aim of this study was to assess the efficacy of glycopyrronium bromide as compared with scopolamine hydrobromide in alleviating death rattle in terminal cancer patients with cognitive impairment. In a randomized, controlled study design patients were allocated in two groups. Group A received scopolamine hydrobromide in a dose of 0.5 mg intravenously every 6 hours for a period of 12 hours, group B received glycopyrronium bromide 0.4 mg every 6 hours for a period of 12 hours. In addition, standardized sedatives were administered as required and the analgesic therapy continued either orally or, if necessary, subcutaneously or intravenously in equipotent doses. Every 2 hours death rattle was assessed and rated on a scale of 1 to 5 (1 = audible breathing noises, 5 = very severe rattling noises). In addition, restlessness and expressions of pain were assessed and rated on a scale of 1 to 3 (1 = mild, 2 = moderate, 3 = severe). 13 patients were included in the study, 7 patients were allocated to group A and 6 patients to group B. There were no significant differences in demographic data, age, weight and diagnosis distribution between the two groups. Group B demonstrated a significant reduction of death rattle in the first 12 hours (p = 0.029) in comparison to group A. There were no significant differences concerning the side effects (restlessness, expressions of pain) in both groups. Glycopyrronium bromide given in a dose of 0,4 mg every six hours demonstrated a significant reduction of death rattle compared to scopolamine hydrobromide. Concerning side effects (restlessness, expressions of pain) there was no difference between both substances.

  19. Ameliorative effects of amide derivatives of 1,3,4-thiadiazoles on scopolamine induced cognitive dysfunction.

    PubMed

    Kulshreshtha, Akanksha; Piplani, Poonam

    2016-10-21

    The present study reports the effect of amide derivatives of 1,3,4-thiadizoles on scopolamine induced deficit cholinergic neurotransmission and oxidative stress serving as promising leads for the therapeutics of cognitive dysfunction. Fourteen compounds (2c-8d) have been synthesised and evaluated against behavioural alterations using step down passive avoidance protocol and morris water maze and at a dose of 0.5 mg/kg with reference to the standard, Rivastigmine. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione, plasma nitrite, catalase) has also been carried out to assess the role of synthesised molecules on the oxidative damage induced by scopolamine. The compounds 5c, 6c and 8c displayed appreciable activity with an IC50 value of 3 μM, 3.033 μM and 2.743 μM, respectively towards acetylcholinesterase inhibition. These compounds also decreased scopolamine induced oxidative stress, thus serving as promising leads for the amelioration of oxidative stress induced cognitive decline. The molecular docking study performed to predict the binding mode of the compounds also suggested that these compounds bind appreciably with the amino acids present in the active site of recombinant human acetylcholinesterase (rhAChE). The results indicated that these compounds could be further traversed as inhibitors of AChE and oxidative stress for the treatment of cognitive dysfunction.

  20. Drug-induced hyperthermic syndromes: part I. Hyperthermia in overdose.

    PubMed

    Hayes, Bryan D; Martinez, Joseph P; Barrueto, Fermin

    2013-11-01

    Drugs and natural compounds that affect the thermoregulatory system can induce or contribute to hyperthermia when used in excess. Hyperthermia associated with drug overdose is dangerous and potentially lethal. This article reviews the body's process of maintaining thermodynamic equilibrium, and describes the mechanisms by which it is influenced by sympathomimetic and anticholinergic drugs, salicylates, and thyroid replacement medications. Appropriate treatment strategies such as cooling and the administration of counteractive medications are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.