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Sample records for anticholinergic drugs scopolamine

  1. DFT-GIAO(1)H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (-)-scopolamine and (-)-hyoscyamine.

    PubMed

    Muñoz, Marcelo A; Joseph-Nathan, Pedro

    2010-06-01

    The relatively large chemical shift differences observed in the (1)H NMR spectra of the anticholinergic drugs (-)-scopolamine 1 and (-)-hyoscyamine 2 measured in CDCl(3) are explained using a combination of systematic/molecular mechanics force field (MMFF) conformational searches and gas-phase density functional theory (DFT) single point calculations, geometry optimizations and chemical shift calculations within the gauge including/invariant atomic orbital (GIAO) approximation. These calculations show that both molecules prefer a compact conformation in which the phenyl ring of the tropic ester is positioned under the tropane bicycle, clearly suggesting that the chemical shift differences are produced by the anisotropic effect of the aromatic ring. As the calculations fairly well predict these experimental differences, diastereotopic NMR signal assignments for the two studied molecules are proposed. In addition, a cursory inspection of the published (1)H and (13)C NMR spectra of different forms of 1 and 2 in solution reveals that most of them show these diastereotopic chemical shift differences, strongly suggesting a preference for the compact conformation quite independent of the organic or aqueous nature of the solvent.

  2. 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.

  3. 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.

  4. [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. PMID:25087132

  5. 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.

  6. 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. PMID:26119520

  7. 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.

  8. Effect of purification followed by solubilization of receptor material on quantitative receptor assays for anticholinergic drugs.

    PubMed

    Smisterová, J; Ensing, K; de Zeeuw, R A

    1996-08-01

    In order to optimize quantitative receptor assays for anticholinergics, the different receptor preparations resulting from the purification and the solubilization of the P2 pellet from the calf striatum were evaluated. The dissociation constants for two chemically different anticholinergics, the tertiary amine scopolamine and the quaternary amine oxyphenonium, were calculated from inhibition studies of 3H-NMS binding in buffer and plasma. The Kd values for both anticholinergics were similar for all the membrane-bound receptor preparations (unpurified and the purified P2 pellet) either in buffer or in plasma. More pronounced differences were observed between the membrane-bound and solubilized receptors. By introducing the solubilized receptor as well, differences between the individual anticholinergics appeared. On the one hand, for scopolamine, a gain in sensitivity of 1.5-2.8 in plasma was observed for the solubilized receptor. On the other hand, in the case of oxyphenonium, a dramatic loss in sensitivity (by a factor of about 24) was observed with the solubilized receptor, as compared to the membrane-bound receptor, in buffer. Very interestingly, however, when the solubilized receptor was used in plasma, a lowering of the Kd value was found for both anticholinergics, i.e. the assays became more sensitive. Such an effect (not observed for the membrane-bound receptor) could be obtained only when the percentage of digitonin present in the assay was at least 0.12% (w/v) or higher. PMID:8877848

  9. 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.

  10. [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.

  11. The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study

    PubMed Central

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

    2009-01-01

    AIMS The use of anticholinergic antiparkinson drugs is assumed to have shifted from the therapy of Parkinson's disease to the amelioration of extrapyramidal adverse effects induced by antipsychotic drugs. There is a considerable body of data suggesting that anticholinergic antiparkinson drugs have a potential for abuse. The aim was to investigate the use and potential abuse of this class of drugs in Norway. METHODS Data were drawn from the Norwegian Prescription Database on sales to a total of 73 964 patients in 2004 of biperiden and orphenadrine, and use in patients with Parkinson's disease or in patients who were also prescribed antipsychotic agents. Possible abuse of these drugs was assessed by the level of use, skewedness of use, indications of drug-seeking behaviour and concomitant use of benzodiazepine tranquillizers, a group of prescription drugs with a recognized potential for abuse. RESULTS Anticholinergic antiparkinson drugs were prescribed to 4.5% of all outpatients who used antipsychotic drugs. This outnumbered sales to patients with Parkinson's disease by >20 to 1. We found indications of abuse of benzodiazepine tranquillizers among patients using antipsychotics, but there were no clear indications of abuse of anticholinergics, even among patients who were strongly suspected of abuse of benzodiazepines. CONCLUSIONS Anticholinergic antiparkinson drugs were used primarily by patients with psychotic illnesses. These patients have a very high prevalence of legal and illegal drug abuse, but the risk of abuse of anticholinergic antiparkinson drugs seemed small. PMID:19094158

  12. 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.

  13. Effects of selected anticholinergics on acoustic startle response in rats.

    PubMed

    Sipos, M L; Burchnell, V; Galbicka, G

    2001-12-01

    The present study compared the effects of the anticholinergics aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide and trihexyphenidyl hydrochloride on acoustic startle response in rats. Peak startle amplitude, latency to peak startle amplitude and prepulse inhibition following 100- and 120-dB tones were recorded 15 min following drug administration in food-restricted rats. Aprophen, atropine, azaprophen, benactyzine, biperiden and scopolamine significantly increased peak startle amplitude and decreased latency to peak startle amplitude following 100-dB pulses. In contrast, only biperiden increased peak startle amplitude following 120-dB pulses, whereas atropine and trihexyphenidyl decreased latency to peak startle amplitude following 120-dB pulses. Benactyzine decreased prepulse inhibition following both 100- and 120-dB pulses, whereas both biperiden and scopolamine decreased prepulse inhibition following 120-dB pulses. Acoustic startle response measures were effective in differentiating the effects of anticholinergic compounds. The comparison of drug effects on the acoustic startle response may be useful in selecting efficacious anticholinergic drug therapies with a minimal range of side-effects. In addition, these data may be useful in down-selecting the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests. PMID:11920928

  14. 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.

  15. The effects of scopolamine on extinction and spontaneous recovery.

    PubMed

    Morley, B J; Russin, R

    1978-04-11

    The effects of scopolamine hydrobromide on baseline extinction levels and spontaneous recovery were assessed. Rats were trained on one of four reinforcement schedules (CRF, FR 10, FR 20, FR 40) with either food or water reinforcement. Scopolamine increased response rates in extinction and spontaneous recovery following training on all four schedules when the reinforcer was water, but had no effect on responding previously maintained by food. The results are discussed in terms of the limitations of a general theory of a cholinergic system mediating all suppressed behavior and the effects of anticholinergic drugs on central thirst mechanisms and consummatory behavior.

  16. 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

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

    PubMed

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

    2014-08-01

    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

  18. Concordance among anticholinergic burden scales

    PubMed Central

    Naples, Jennifer G.; Marcum, Zachary A.; Perera, Subashan; Gray, Shelly L.; Newman, Anne B.; Simonsick, Eleanor M.; Yaffe, Kristine; Shorr, Ronald I.; Hanlon, Joseph T.

    2015-01-01

    Background There is no gold standard to assess potential anticholinergic burden of medications. Objectives To evaluate concordance among five commonly used anticholinergic scales. Design Cross-sectional secondary analysis. Setting Pittsburgh, PA, and Memphis, TN. Participants 3,055 community-dwelling older adults aged 70–79 with baseline medication data from the Health, Aging, and Body Composition study. Measurements Any use, weighted scores, and total standardized daily dosage were calculated using five anticholinergic measures (i.e., Anticholinergic Cognitive Burden [ACB] Scale, Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Drug Burden Index anticholinergic component [DBI-ACh], and Summated Anticholinergic Medications Scale [SAMS]). Concordance was evaluated with kappa statistics and Spearman rank correlations. Results Any anticholinergic use in rank order was 51% for the ACB, 43% for the ADS, 29% for the DBI-ACh, 23% for the ARS, and 16% for the SAMS. Kappa statistics for all pairwise use comparisons ranged from 0.33 to 0.68. Similarly, concordance as measured by weighted kappa statistics ranged from 0.54 to 0.70 among the three scales not incorporating dosage (ADS, ARS, and ACB). Spearman rank correlation between the DBI-ACh and SAMS was 0.50. Conclusions Only low to moderate concordance was found among the five anticholinergic scales. Future research is needed to examine how these differences in measurement impact their predictive validity with respect to clinically relevant outcomes, such as cognitive impairment. PMID:26480974

  19. 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.

  20. 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.

  1. Efficacy of injectable anticholinergic drugs against soman-induced convulsive/subconvulsive activity.

    PubMed

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

    1994-01-01

    Six FDA approved, injectable compounds [benztropine (BZT); biperiden (BIP); dicyclomine (DCL); l-hyoscyamine (HYO); orphenadrine (ORP); scopolamine (SCP)] were each compared to diazepam (DZ, the standard) in male guinea pigs against ongoing soman-induced convulsive or sub-CV (CV/sub-CV) activity. Three trained graders concurrently assigned CV/sub-CV scores to each animal based on signs of intoxication at various times post-soman. Animals received (im) pyridostigmine (26 micrograms/kg) 30 min before soman (56 micrograms/kg; 2 x 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 was assured. BIP and SCP were effective 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 the most effective dosages of SCP (1.0 mg/kg) and BIP (10 mg/kg), the CV/sub-CV scores were significantly lower (p < 0.05) than those of DZ. Only 33% survival was observed at each of two doses of ORP and one dose of HYO; therefore, no further testing was done with these compounds. Using freshly prepared solutions, DCL (up to 40 mg/kg) and BZT (up to 96 mg/kg) were tested with mixed results; DCL lowered lethality while BZT increased lethality. CV/sub-CV scores for the most effective dose of DCL and BZT were, however, lower than those of DZ. SCP is an antimuscarinic drug devoid of antinicotinic activity, while BIP possesses antimuscarinic, antinicotinic, antispasmodic and anti-N-methyl-D-aspartate activity. Recent evidence suggests that, in late stages of intoxication by nerve agents, noncholinergic, excitatory amino acid receptors may become involved and necessitate the use of a multi-action drug like BIP. The findings herein suggest that SCP and BIP are superior to DZ, but further studies are needed to determine which drug or drug class should be pursued in more advanced testing.

  2. 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.

  3. Caramiphen and scopolamine prevent soman-induced brain damage and cognitive dysfunction.

    PubMed

    Raveh, Lily; Weissman, Ben Avi; Cohen, Giora; Alkalay, David; Rabinovitz, Ishai; Sonego, Hagar; Brandeis, Rachel

    2002-05-01

    Exposure to soman, a toxic organophosphate nerve agent, causes severe adverse effects and long term changes in the peripheral and central nervous systems. The goal of this study was to evaluate the ability of prophylactic treatments to block the deleterious effects associated with soman poisoning. scopolamine, a classical anticholinergic agent, or caramiphen, an anticonvulsant anticholinergic drug with anti-glutamatergic properties, in conjunction with pyridostigmine, a reversible cholinesterase inhibitor, were administered prior to sbman (1 LD50). Both caramiphen and scopolamine dramatically attenuated the process of cell death as assessed by the binding of [3H]RoS-4864 to peripheral benzodiazepine receptors (omega3 sites) on microglia and astrocytes. In addition, caramiphen but not scopolamine, blocked the soman-evoked down-regulation of [3H]AMPA binding to forebrain membrane preparations. Moreover, cognitive tests utilizing the Morris water maze, examining learning and memory processes as well as reversal learning, demonstrated that caramiphen abolished the effects of soman intoxication on learning as early as the first trial day, while scopolamine exerted its effect commencing at the second day of training. Whereas the former drug completely prevented memory deficits, the latter exhibited partial protection. Both agents equally blocked the impairment of reversal learning. In addition, there is a significant correlation between behavioral parameters and [3H]RoS-4864 binding to forebrain membrane preparations of rats, which participated in these tests (r(21) = 0.66, P < 0.001; r(21) = 0.66, P < 0.001, -0.62, P < 0.002). These results demonstrate the beneficial use of drugs exhibiting both anti-cholinergic and anti-glutamatergic properties for the protection against changes in cognitive parameters caused by nerve agent poisoning. Moreover, agents such as caramiphen may eliminate the need for multiple drug therapy in organophosphate intoxications.

  4. 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.

  5. 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.

  6. [Central anticholinergic syndrome].

    PubMed

    Fernández Urretavizcaya, P; Cenoz Osinaga, J C; Jáuregui Garía, M L; Gállego Culleré, J

    1991-10-01

    Two new cases of anticolinergic central syndrome are described. The first case, a 8 year old girl, suffered a severe encefalopathy after topical application of mydriatic cholirio as an aid in a rutine study of ocular refraction. The second case, 67 year old man presented a severe neurological picture after accidental intake of a silvester plantground (Atropa belladonna). His neurological condition returned quickly to normal whith administration of physostigmine. Differents aspects of the etiology, clinical picture and diagnosis are discussed with special emphasis in patients with delirium or acute confusional states. Finally, attention is drawn in the necessity of a properly use of anticholinergic drugs overcoat in aged or children.

  7. 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

  8. 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.

  9. 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.

  10. Atropine, an anticholinergic drug, impairs memory retrieval of a high consolidated avoidance response in mice.

    PubMed

    Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B; Baratti, Carlos M

    2003-07-17

    Immediate post-training intraperitoneal administration of the centrally acting anticholinesterase physostigmine (70.0, or 150.0 microg/kg) enhanced retention of male CF-1 mice tested 48 h after training in a one-trial step-through inhibitory avoidance task (0.8 mA, 50 Hz, 1 s footshock). The effect was observed in mice that received saline 30 min before the retention test; on the contrary, the pre-test administration of the centrally active muscarinic cholinergic antagonist, atropine (1.0 mg/kg, i.p.), but not methylatropine (1.0 mg/kg, i.p.), instead of saline, prevents the enhancement of retention induced by both doses of the anticholinesterase when given immediately after training. The high retention performance caused by post-training physostigmine was recovered following a second administration of the same doses of the drug, 10 min after the pre-test injections of atropine. Since, physostigmine do not influence memory retrieval when given prior to the retention test, and its post-training effects are not due to the induction of state-dependency, the recover of the high retention performance was probably due to a classical interaction between a muscarinic competitive antagonist and an indirect cholinergic agonist. Further, atropine probably does not modify the memory trace by erasing it, but by producing a poor retrieval. PMID:12821180

  11. Atropine, an anticholinergic drug, impairs memory retrieval of a high consolidated avoidance response in mice.

    PubMed

    Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B; Baratti, Carlos M

    2003-07-17

    Immediate post-training intraperitoneal administration of the centrally acting anticholinesterase physostigmine (70.0, or 150.0 microg/kg) enhanced retention of male CF-1 mice tested 48 h after training in a one-trial step-through inhibitory avoidance task (0.8 mA, 50 Hz, 1 s footshock). The effect was observed in mice that received saline 30 min before the retention test; on the contrary, the pre-test administration of the centrally active muscarinic cholinergic antagonist, atropine (1.0 mg/kg, i.p.), but not methylatropine (1.0 mg/kg, i.p.), instead of saline, prevents the enhancement of retention induced by both doses of the anticholinesterase when given immediately after training. The high retention performance caused by post-training physostigmine was recovered following a second administration of the same doses of the drug, 10 min after the pre-test injections of atropine. Since, physostigmine do not influence memory retrieval when given prior to the retention test, and its post-training effects are not due to the induction of state-dependency, the recover of the high retention performance was probably due to a classical interaction between a muscarinic competitive antagonist and an indirect cholinergic agonist. Further, atropine probably does not modify the memory trace by erasing it, but by producing a poor retrieval.

  12. 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

    ... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as... ingredient. The belladonna alkaloids, which contain atropine (d, dl hyoscyamine) and scopolamine (l- hyoscine... ingredients as an anticholinergic for cough-cold use. Belladonna alkaloids for inhalation use, as contained...

  13. 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

    ... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as... ingredient. The belladonna alkaloids, which contain atropine (d, dl hyoscyamine) and scopolamine (l- hyoscine... ingredients as an anticholinergic for cough-cold use. Belladonna alkaloids for inhalation use, as contained...

  14. 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

    ... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as... ingredient. The belladonna alkaloids, which contain atropine (d, dl hyoscyamine) and scopolamine (l- hyoscine... ingredients as an anticholinergic for cough-cold use. Belladonna alkaloids for inhalation use, as contained...

  15. 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

    ... in cough-cold drug products. (a) Atropine sulfate, belladonna alkaloids, and belladonna alkaloids as... ingredient. The belladonna alkaloids, which contain atropine (d, dl hyoscyamine) and scopolamine (l- hyoscine... ingredients as an anticholinergic for cough-cold use. Belladonna alkaloids for inhalation use, as contained...

  16. Locomotor stereotypy produced by dexbenzetimide and scopolamine is reduced by SKF 83566, not sulpiride.

    PubMed

    Fritts, M E; Mueller, K; Morris, L

    1998-07-01

    Like amphetamine, scopolamine produces locomotor stereotypy (repetitive routes of locomotion) in an open field. To determine whether locomotor stereotypy is a common behavioral effect of anticholingeric agents, several doses of the anticholinergic dexbenzetimide were tested for the ability to produce locomotor stereotypy; like scopolamine, dexbenzetimide produced locomotor stereotypy. To investigate a possible role of dopamine in anticholinergic-induced locomotor stereotypy, we tested the ability of the dopamine D1 antagonist SKF 83566 and the D2 antagonist sulpiride to block the locomotor stereotypy induced by scopolamine as well as dexbenzetimide. SKF 83566 blocked scopolamine- and dexbenzetimide-induced locomotor stereotypy; sulpiride did not reduce dexbenzetimide-induced locomotor stereotypy, but enhanced scopolamine-induced locomotor stereotypy. Hyperlocomotion was reduced by both dopamine antagonists. Results are interpreted in support of the notion that dopamine is the likely candidate mediating locomotor stereotypy. PMID:9678647

  17. 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.

  18. Comparative behavioral effects of anticholinergic agents in cats: psychomotor stimulation and aggression.

    PubMed

    Beleslin, D B; Stefanović-Denić, K; Samardzić, R

    1986-03-01

    The effect on behavior of eight anticholinergic agents: atropine, scopolamine, trihexyphenidyl, biperiden, homatropine, eucatropine, hexocyclium and propantheline, injected into the cerebral ventricle (ICV) of the cat was investigated and compared. The anticholinergic agents evoked: (1) psychomotor stimulation such as miaowing, loud calling, restlessness, impelling locomotion, jumping, vacant staring, apprehension and loss of interest of the surroundings; (2) aggression, hissing, threat, attack, defense, fighting with paws and flight; (3) autonomic responses including mydriasis, tachypnea, dyspnea, licking, vomiting, salivation, micturition and defection; and (4) motor phenomena comprising scratching, ataxia, rigidity, tremor, weakness with adynamia or myoclonic jerks. Convulsions appeared only after ICV injections of atropine and homatropine. The most characteristic behavioral effect of anticholinergic agents was psychomotor stimulation accompanied by mild aggressive responses. The only exception was propantheline which caused a muscular weakness and adynamia. Atropine and scopolamine alone induced a dose-dependent impelling locomotion as well as fighting behavior. Carbachol and eserine injected intracerebroventricularly reversed the locomotion autonomic and motor phenomena produced by anticholinergic agents administered similarly. It is suggested that anticholinergic agents acting as partial agonists, can produce their behavioral effects through central cholinoceptive sites. PMID:3703893

  19. 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.

  20. 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.

  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. [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. PMID:27025142

  3. [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.

  4. 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.

  5. Examination and Estimation of Anticholinergic Burden: Current Trends and Implications for Future Research.

    PubMed

    Salahudeen, Mohammed Saji; Nishtala, Prasad S

    2016-05-01

    It is postulated that minimizing anticholinergic burden in older people may result in improved short-term memory and behavior, reduced confusion and delirium, and enhanced quality of life and daily functioning. The purpose of this opinion article was to investigate the current trends and future implications relating to the examination and estimation of anticholinergic burden in older people. Current evidence linking medicines with anticholinergic activity and cognitive impairment is derived mostly from observational data. Further research with larger trials or cohort studies with adequate power and appropriate follow-up periods is required to confirm associations between anticholinergic burden and adverse outcomes. This article provides insights into different approaches for the estimation of anticholinergic burden. Network-based systems pharmacology models could be an effective way of understanding anticholinergic drug-induced adverse effects. The emphasis on mechanistic models may open new opportunities for researchers to understand adverse drug effects in clinical practice. In the interim, medicines with high anticholinergic activity should be avoided in older people, unless considered clinically essential. In this instance, they should be used at a low/titrated dose and for the shortest duration possible. It is therefore important to reinforce the clinical significance of reviewing anticholinergic medicines in older people. PMID:27038065

  6. 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.

  7. Cumulative Use of Strong Anticholinergic Medications and Incident Dementia

    PubMed Central

    Gray, Shelly L.; Anderson, Melissa L.; Dublin, Sascha; Hanlon, Joseph T.; Hubbard, Rebecca; Walker, Rod; Yu, Onchee; Crane, Paul; Larson, Eric B.

    2015-01-01

    IMPORTANCE Many medications have anticholinergic effects. The general view is that anticholinergic-induced cognitive impairment is reversible upon medication discontinuation. However, a few studies suggest that anticholinergic medications may be associated with increased dementia risk. OBJECTIVE To examine whether cumulative anticholinergic medication use is associated with a higher risk of incident dementia. DESIGN Prospective population-based cohort study using data from the Adult Changes in Thought Study. SETTING Group Health, an integrated health-care delivery system, Seattle, Washington PARTICIPANTS 3,434 participants aged 65 and older with no dementia at study entry. Initial recruitment occurred between 1994 and 1996 or 2000 and 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants received follow-up every two years. EXPOSURE Using computerized pharmacy dispensing data, cumulative anticholinergic exposure was defined as the total standardized daily doses (TSDD) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was time-varying. MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer’s disease using standard diagnostic criteria. Statistical analyses used Cox proportional hazards models, adjusted for demographic, health behaviors and health status including comorbidities. RESULTS The most common anticholinergic drug classes used were tricyclic antidepressants, first generation antihistamines and bladder antimuscarinics. Over a mean follow-up of 7.3 years, 797 participants (23%) developed dementia (637 developed Alzheimer’s). A 10-year cumulative dose-response relationship was observed for both dementia and Alzheimer’s disease (test for trend, p<0.001). For dementia, adjusted hazard ratios (HRs) and 95% confidence interval (CI) for cumulative anticholinergic use was 0.92 (95% CI, 0.74-1.16) for 1-90 TSDD; 1.19 (CI, 0.94-1.51) for

  8. 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

  9. 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

  10. 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; ...

  11. 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.

  12. Scopolamine blocks the effects of swim stress on memory retrieval in rats.

    PubMed

    Kumar, K B; Karanth, K S

    1996-01-01

    This study examined whether application of swim stress improved retrieval of a passive avoidance memory and if pretreatment with the anticholinergic agent, scopolamine, blocked this effect on memory retrieval. Animals initially given a passive avoidance training session were subjected to either a two or four swim stress sessions (15 min each) with or without prior treatment of scopolamine (0.05 or 0.1 mg/kg). The retrieval performance in passive avoidance test and motor activity was assessed 24 hr after the last swim stress session. In an independent control experiment, the passive avoidance training and test were conducted respectively, 24 and 72 hr after the last of four swim stress sessions with or without prior injection of scopolamine (0.1 mg/kg). The results showed an enhanced performance for the passive avoidance task in rats subjected to four swim stress sessions in both experiments and scopolamine given 30 min prior to each stress session diminished this performance of animals in the passive avoidance test. Two swim stress sessions with or without scopolamine treatment caused no significant effects on the retrieval performance. Also, no significant difference was observed among the groups in motor activity following any of the stress treatments in the open field test. These results, thus suggested for the first time, a relationship among swim stress, cholinergic activity and avoidance memory processes.

  13. Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men

    PubMed Central

    Han, Ling; Agostini, Joseph V.; Allore, Heather G.

    2014-01-01

    OBJECTIVES To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men. DESIGN Prospective cohort study. SETTING A Department of Veterans Affairs primary care clinic. PARTICIPANTS Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension. MEASUREMENTS The outcomes were measured using the Hopkins Verbal Recall Test (HVRT) for short-term memory and the instrumental activity of daily living (IADL) scale for executive function at baseline and during follow-up. Anticholinergic medication use was ascertained using participants' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anti-cholinergic score. RESULTS Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs. On average, a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point (95% confidence interval (CI) = 0.05–0.58) and 0.10-point (95% CI = 0.04–0.17) decrease in the HVRT and IADLs, respectively, independent of other potential risk factors for cognitive impairment, including age, education, cognitive and physical function, comorbidities, and severity of hypertension. The association was attenuated but remained statistically significant with memory (0.29, 95% CI = 0.01–0.56) and executive function (0.08, 95% CI = 0.02–0.15) after further adjustment for concomitant non-anticholinergic medications. CONCLUSION Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men. Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects. PMID:19093918

  14. 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. PMID:24169716

  15. 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.

  16. 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.

  17. An overlooked effect of systemic anticholinergics: alteration on accommodation amplitude

    PubMed Central

    Sekeroglu, Mehmet Ali; Hekimoglu, Emre; Anayol, Mustafa Alpaslan; Tasci, Yasemin; Dolen, Ismail

    2016-01-01

    AIM To investigate the effect of oral solifenacin succinate, tolterodine-L-tartarate and oxybutinin hydrochloride (HCl) on accommodation amplitude. METHODS Female overactive bladder syndrome (OAB) patients who were planned to use oral anticholinergics, patients that uses solifenacin succinate 5 mg (Group I, n=25), tolterodine-L-tartarate 4 mg (Group II, n=25), and oxybutinin HCl 5 mg b.i.d (Group III, n=25) and age matched healthy female subjects (Group IV, n=25) were recruited and complete ophthalmological examination and accommodation amplitude assessment were done at baseline and 4wk after initiation of treatment. RESULTS The mean age of 100 consecutive female subjects was 51.6±5.7 (40-60)y and there were no statistically significant difference with regard to the mean age (P=0.107) and baseline accommodation amplitude (P=0.148) between study groups. All treatment groups showed a significant decrease in accommodation amplitude following a 4-week course of anticholinergic treatment (P=0.008 in Group I, P=0.002 in Group II, P=0.001 in Group III), but there was no statistically significant difference in Group IV (P=0.065). CONCLUSION A 4-week course of oral anticholinergic treatment have statistically significant effect on accommodation amplitude. Clinicians should avoid both overestimating this result, as this would unnecessarily restrict therapeutic possibilities, and also underestimating it which may lead to drug intolerance. PMID:27275433

  18. Effect of orally administered 15(R)-15-methyl prostaglandin E2 and/or an anticholinergic drug on meal-induced gastric acid secretion and serum gastrin level in patients with duodenal ulcers.

    PubMed

    Konturek, S J; Swierczek, J S; Kwiecien, N; Obtułowicz, W; Sito, E; Oleksy, J

    1979-01-01

    The purpose of the present series of tests was to measure and compare the effects of ingestion of gelatin capsules containing 15(R)-15-methyl PGE2 (PG) and/or an anticholinergic drug (methscopolamine bromide, Pamine) on meal-induced gastric acid secretion and serum gastrin level. Eleven duodenal ulcer patients were stimulated by a 5% peptone meal. Acid secretion was determined by the intragastric titration technique, and serum gastrin was measured by radioimmunoassay. The tests were randomized and double-blind. PG alone given 30 min before a test meal at a dose of 50 micrograms or 100 micrograms produced no side effects and inhibited meal-stimulated acid secretion by about 43% and 55%, respectively. Gastric acid inhibition after a single dose of PG was most pronounced in the first hour of a test meal and was accompanied by almost complete suppression of the meal-induced serum gastrin level. Pamine alone in a dose of 2.5 mg reduced gastric acid response to a meal by about 29% but caused a further rise of postprandial serum gastrin level over control values. The combination of PG, 50 micrograms, and Pamine, 2.5 mg, did not result in significantly greater acid inhibition (about 48%) than when either compound was given alone. When the higher dose of PG (100 micrograms) was given together with Pamine (2.5 mg), the degree of inhibition produced by PG alone was not changed. It is concluded that PG given orally in capsules is a potent inhibitor of gastric acid and serum gastrin response to a meal and that this effect may be of potential value in the treatment of peptic ulcer disease.

  19. Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong.

    PubMed

    Chan, Thomas Y K

    2016-03-01

    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

  20. 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.

  1. 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).

  2. 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). PMID:25248046

  3. Anticholinergic Medication Use and Risk of Fracture in Elderly Adults with Depression.

    PubMed

    Chatterjee, Satabdi; Bali, Vishal; Carnahan, Ryan M; Chen, Hua; Johnson, Michael L; Aparasu, Rajender R

    2016-07-01

    Limited research exists regarding the effect of anticholinergics on falls and fractures in elderly nursing home residents in the United States. This study examined the risk of fractures associated with anticholinergic medication use in elderly nursing home residents with depression. A nested case-control design involving a cohort of elderly adults with depression from the 2007 to 2010 Minimum Data Set (MDS)-linked Medicare data was used to evaluate the risk of fractures. The study sample included Medicare beneficiaries aged 65 and older diagnosed with depression having at least one nursing home stay during 2007 to 2010 and no history of falls or fractures in 2007 (base period). Cases were individuals with incident fractures after the baseline period. For each case, four age- and sex-matched controls were selected using incidence density sampling. Anticholinergic exposure was defined using the Anticholinergic Drug Scale (ADS). Prescription of Level 2 or 3 anticholinergic medications within 30 days before the event date was the primary exposure. The primary outcome was an inpatient or outpatient claim for a fracture between January 1, 2008, and December 31, 2010. A conditional logistic regression model stratified on matched case-control sets was used to evaluate association between anticholinergic use and fractures, controlling for other risk factors of the outcome. The study sample consisted of 40,452 individuals with fractures and 161,808 matched controls. After adjusting for other risk factors, high-level anticholinergic use was associated with 14% greater fracture risk than nonuse (odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.11-1.17). The high risk of fractures remained consistent across levels of anticholinergic potency (Level 2, OR = 1.15, 95% CI = 1.11-1.19; Level 3, OR = 1.10, 95% CI = 1.07-1.15). The study findings remained consistent in multiple sensitivity analyses. Overall, use of high-level anticholinergic medications was associated with

  4. Chronic Anticholinergic Use and the Aging Brain

    PubMed Central

    Cai, Xueya; Campbell, Noll; Khan, Babar; Callahan, Chris; Boustani, Malaz

    2012-01-01

    Background Older Americans are facing an epidemic of chronic diseases and are thus exposed to anticholinergics (AC) that might negatively affect their risk of developing mild cognitive impairment (MCI) or dementia. Objective Investigate the association between impairment in cognitive function and previous AC exposure. Design A retrospective cohort study. Setting Primary care clinics in Indianapolis, Indiana. Participants 3690 older adults who have undergone cognitive assessment and had a one-year medication dispensing record. Outcome Cognitive function was measured in two sequential steps; a two-step screening process followed by a formal diagnostic process for participants with positive screening results. Exposure Three patterns of AC exposure were defined by the duration of AC exposure, the number of AC medications dispensed at the same time, and the severity of AC effects as determined by the Anticholinergic Cognitive Burden List. Results In comparison to older adults with no anticholinergic exposure and after adjusting for age, race, gender, and underlying comorbidity, the odds ratio (OR) for having a diagnosis of MCI was 2.73 (95% confidence interval, CI; 1.27, 5.87) among older adults who were exposed to at least three possible anticholinergic for at least 90 days; and the OR for having dementia was 0.43 (95% CI; 0.10, 1.81). Conclusion Exposure to medications with severe anticholinergic cognitive burden may be a risk factor for developing MCI. PMID:23183138

  5. Impact of antipsychotics and anticholinergics on autonomic modulation in patients with schizophrenia.

    PubMed

    Huang, Wei-Lieh; Chang, Li-Ren; Kuo, Terry B J; Lin, Yu-Hsuan; Chen, Ying-Zai; Yang, Cheryl C H

    2013-04-01

    Antipsychotics are associated with cardiovascular risk, but the relationship between their anticholinergic properties and cardiac function is not clear. We hypothesize that antipsychotics with a high muscarinic affinity (HMA) may reduce parasympathetic modulation, which should be observable by means of heart rate variability (HRV) measurement. We also assume that anticholinergics, which are commonly used in patients with schizophrenia to treat drug-induced parkinsonism, interact with antipsychotics, and this may also affect HRV. Fifty-five patients with schizophrenia were recruited into this study. Twenty-eight subjects used antipsychotics with an HMA and 27 subjects used antipsychotics with a low muscarinic affinity (LMA). Heart rate variability values between the patients on antipsychotics with HMA and those on antipsychotics with LMA were compared. Correlation and regression analysis were then performed to clarify the relationship between HMA, LMA, and HRV. The influence of anticholinergics was also assessed by correlation analysis. The HMA group showed significantly reduced low-frequency (LF) power, high-frequency (HF) power, total power (TP), and normalized LF (LF%) than the LMA group. Regression analysis supported the hypothesis that muscarinic affinity was related to LF (β = -0.447; P < 0.001), HF (β = -0.390; P = 0.002), and TP (β = -0.399; P = 0.001). The interaction between LMA and anticholinergic use also influenced LF% (β = 0.326; P = 0.006). In the LMA group, the use of anticholinergics was positively correlated with LF% and LF/HF. In the HMA group, after exclusion of the patients using anticholinergics, the equivalent dose of antipsychotics showed a negative correlation with HF. Our results suggest that the muscarinic affinity of antipsychotics affects both sympathetic and parasympathetic modulation and that anticholinergics interact with antipsychotics to influence HRV.

  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. Pharmacological management of anticholinergic delirium - theory, evidence and practice.

    PubMed

    Dawson, Andrew H; Buckley, Nicholas A

    2016-03-01

    The spectrum of anticholinergic delirium is a common complication following drug overdose. Patients with severe toxicity can have significant distress and behavioural problems that often require pharmacological management. Cholinesterase inhibitors, such as physostigmine, are effective but widespread use has been limited by concerns about safety, optimal dosing and variable supply. Case series support efficacy in reversal of anticholinergic delirium. However doses vary widely and higher doses commonly lead to cholinergic toxicity. Seizures are reported in up to 2.5% of patients and occasional cardiotoxic effects are also recorded. This article reviews the serendipitous path whereby physostigmine evolved into the preferred anticholinesterase antidote largely without any research to indicate the optimal dosing strategy. Adverse events observed in case series should be considered in the context of pharmacokinetic/pharmacodynamic studies of physostigmine which suggest a much longer latency before the maximal increase in brain acetylcholine than had been previously assumed. This would favour protocols that use lower doses and longer re-dosing intervals. We propose based on the evidence reviewed that the use of cholinesterase inhibitors should be considered in anticholinergic delirium that has not responded to non-pharmacological delirium management. The optimal risk/benefit would be with a titrated dose of 0.5 to 1 mg physostigmine (0.01-0.02 mg kg(-1) in children) with a minimum delay of 10-15 min before re-dosing. Slower onset and longer acting agents such as rivastigmine would also be logical but more research is needed to guide the appropriate dose in this setting.

  8. Microbore liquid chromatography of tertiary amine anticholinergic pharmaceuticals with tris(2,2'-bipyridine)ruthenium(III) chemiluminescence detection.

    PubMed

    Holeman, J A; Danielson, N D

    1995-06-01

    The post-column chemiluminescent reaction of six anticholinergic alkaloid compounds with tris(2,2'-bipyridine)ruthenium(III) (Ru(bpy)3(3+)) is applied to microbore high-performance liquid chromatography (HPLC). At flow rates less than 200 microL/min, the capillary mixing cell in which Ru(bpy)3(3+) and the analyte are mixed directly allows for good light detection. In contrast, a diminished signal occurs at these low flow rates with conventional post-column mixing in a tee. Optimal chemiluminescent pH conditions for atropine, scopolamine, dicyclomine, cyclopentolate, cyclobenzaprine, and procyclidine are determined at moderately basic conditions (pH 7 to 9). 2-Butanone is found to be compatible with the chemiluminescent reaction, whereas tetrahydrofuran and propionitrile cause an increase in background noise and a chemiluminescent signal loss. As 2-butanone is more nonpolar than acetonitrile, it assists in the elution of these hydrophobic anticholinergic compounds. Five anticholinergic compounds are resolved successfully with a PRP-1 polymeric column and a slightly basic mobile phase, but a C8 silica column is better suited for the more hydrophobic compounds (cyclobenzaprine, procyclidine, and dicyclomine).

  9. 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.

  10. 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. PMID:24188342

  11. 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.

  12. 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.

  13. Scopolamine induced deficits in a battery of rat cognitive tests: comparisons of sensitivity and specificity.

    PubMed

    Hodges, Donald Bartholomew; Lindner, Mark D; Hogan, John B; Jones, Kelly M; Markus, Etan J

    2009-05-01

    Despite much research, the cognitive effects of scopolamine hydrobromide, a cholinergic antagonist, remain controversial. Scopolamine affects multiple systems each of which can impact behavior. One way to tease apart the effects of the drug is to determine the effects of low scopolamine doses on different abilities. The present experiments compared the effects of low doses of scopolamine on a single group of rats conducting a battery of behavioral tasks: Morris water maze, radial arm maze, delayed non-matching to position tasks, and fixed ratio 5 bar pressing. The behavioral battery ranged from tasks having little cognitive demand to those thought to be based more on attention and spatial-working memory. Control experiments using additional groups of rats assessing peripheral versus central effects were conducted with both liquid and dry reinforcement and with methyl scopolamine. Furthermore, the 5-choice serial reaction time test assessed scopolamine effects on attention. The data show a wide spectrum of central and peripheral cholinergic involvement. The central effects include attention and motor initiation, both of which impact and interact with the mnemonic function of acetylcholine. These results show that a limited disruption of the central cholinergic system can have profound effects on attention and/or psychomotor control before any measurable mnemonic disruption.

  14. 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.

  15. Use of inhaled anticholinergic agents in obstructive airway disease.

    PubMed

    Restrepo, Ruben D

    2007-07-01

    In the last 2 decades, anticholinergic agents have been generally regarded as the first-choice bronchodilator therapy in the routine management of stable chronic obstructive pulmonary disease (COPD) and, to a lesser extent, asthma. Anticholinergics are particularly important bronchodilators in COPD, because the vagal tone appears to be the only reversible component of airflow limitation in COPD. The inhaled anticholinergics approved for clinical use are synthetic quaternary ammonium congeners of atropine, and include ipratropium bromide, oxitropium bromide, and tiotropium bromide. This article reviews the most current evidence for inhaled anticholinergics in obstructive airway disease and summarizes outcomes reported in randomized controlled trials.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Anticholinergic substances: A single consistent conformation

    PubMed Central

    Pauling, Peter; Datta, Narayandas

    1980-01-01

    An interactive computer-graphics analysis of 24 antagonists of acetylcholine at peripheral autonomic post-ganglionic (muscarinic) nervous junctions and at similar junctions in the central nervous system, the crystal structures of which are known, has led to the determination of a single, consistent, energetically favorable conformation for all 24 substances, although their observed crystal structure conformations vary widely. The absolute configuration and the single, consistent (ideal) conformation of the chemical groups required for maximum anticholinergic activity are described quantitatively. Images PMID:16592775

  2. The Greater Sensitivity of Elderly APOE ε4 Carriers to Anticholinergic Medications Is Independent of Cerebrovascular Disease Risk

    PubMed Central

    Nebes, Robert D.; Pollock, Bruce G.; Perera, Subashan; Halligan, Edythe M.; Saxton, Judith A.

    2012-01-01

    Background Recent studies found use of anticholinergic medications to be associated with greater performance decrements in older persons who carry an ε4 allele of the apolipoprotein E (APOE) gene than in those carrying only ε2 or ε3 alleles. Objectives The present study examined whether the apparently greater behavioral toxicity of anticholinergic drugs in ε4 carriers may result from an increased risk of cerebrovascular disease, which is more common in ε4 carriers. Methods Cross-sectional data were available from 240 normal elderly [pe1]community volunteers who had participated in 2 different studies of the cognitive and motor effects of normal aging. As part of these studies, information was gathered on subjects' use of anticholinergic medications (based on an inventory of medications taken within 24 hours of testing), risk of cerebrovascular disease (Framingham Stroke Risk Profile), and APOE genotype. Performance data were also available from measures of general cognitive status (Mini-Mental State Examination), executive function (Trail Making Test), mood (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), and walking speed. Logistic and linear regression models were used to examine how outcomes differed between genotypes and drug use, independent of the risk of cerebrovascular disease. Results In persons with a non-ε4 genotype, anticholinergic medication use did not significantly affect any of the behavioral measures. By contrast, among ε4 carriers, those taking anticholinergic drugs performed significantly worse than did those not taking such drugs on tests of general cognitive status, executive function, mood, and sleep. Adjusting for participants' stroke risk had a minimal effect on these results. Conclusions Anticholinergic medication use was associated with poorer performance on measures of cognition, sleep, and mood only in older persons who carried 1 or more ε4 alleles of the APOE gene; this effect did not appear to be the result

  3. 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. PMID:25341608

  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. 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.

  7. 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

  8. 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.

  9. Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats.

    PubMed

    Miczek, K A; Lau, P

    1975-06-19

    It has been postulated that behavioral inhibition due to punishment or extinction may be mediated by brain acetylcholine, and drugs which have disinhibitory action are thought to interact with this system. This notion was tested by comparing the effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption. Scopolamine hydrobromide (0.3, 0.5 mg/kg, i.p.), a centrally and peripherally acting antimuscarinic agent and physostigmine sulfate, (0.3 mg/kg, i.p.), a centrally and peripherally acting acetylcholinesterase inhibitor, lowered both non-punished and punishment suppressed water intake and lick rate, whereas their quaternary analogs which primarily act in the periphery, had no significant effect at comparable dose levels. Scopolamine and physostigmine suppressed punished water consumption at lower dose levels than nonpunished intake. In contrast, chlordiazepoxide (5.0, 10.0, 20.0 mg/kg, i.p.) enhanced punished as well as non-punished water intake. In a further experiment comparing punishment and extinction suppression, scopolamine and physostigmine did not affect punished or extinguished water intake; chlordiazepoxide (5.0, 10.0, 20.0 mg/kg) reliably increased punished, but not extinguished licking on the water nozzle. These results suggest (1) that scopolamine and chlordiazepoxide do not act via a common mechanism, and (2) that punishment and extinction suppression are not a pharmacological entity. PMID:1161984

  10. [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.

  11. 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. PMID:18214292

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Racial Differences in Anticholinergic Use among Community-Dwelling Elders

    PubMed Central

    Felton, Maria; Hanlon, Joseph T.; Perera, Subashan; Thorpe, Joshua M.; Marcum, Zachary A.

    2014-01-01

    Objective Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using prescription and/or non-prescription anticholinergics, a type of potentially inappropriate medication, over time. Design Longitudinal. Setting Health, Aging, and Body Composition Study (years 1, 5, and 10) Participants Three thousand fifty-five black and white community-dwelling older adults at year one Main Outcome Measure Highly anticholinergic medication use as per the 2012 American Geriatrics Society Beers Criteria. Results Blacks represented 41.4% of the participants at year 1. At year 1, 13.4% of blacks used an anticholinergic medication compared to 17.8% of whites, and this difference persisted over the ensuing ten-year period. Diphenhydramine was the most common anticholinergic medication reported at baseline and year 5 and meclizine at year 10 for both races. Controlling for demographics, health status and access to care factors, blacks were 24-45% less likely to use any anticholinergics compared to whites over the years considered (all p<0.05). Conclusion The use of prescription and/or non-prescription anticholinergic medications was less common in older blacks than whites over a ten-year period, and the difference was unexplained by demographics, health status and access-to-care. PMID:25893702

  17. 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

  18. Vascular action as the primary mechanism of cognitive effects of cholinergic, CNS-acting drugs, a rat phMRI BOLD study

    PubMed Central

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

    2014-01-01

    Concordant results of functional magnetic resonance imaging (fMRI) and behavioral tests prove that some non-blood–brain barrier-penetrating drugs produce robust central nervous system (CNS) effects. The anticholinergic scopolamine interferes with learning when tested in rats, which coincides with a negative blood-oxygen-level-dependent (BOLD) change in the prefrontal cortex (PFC) as demonstrated by fMRI. The peripherally acting butylscopolamine also evokes a learning deficit in a water-labyrinth test and provokes a negative BOLD signal in the PFC. Donepezil—a highly CNS-penetrating cholinesterase inhibitor—prevents the negative BOLD and cognitive deficits regardless whether the provoking agent is scopolamine or butylscopolamine. Interestingly, the non-BBB-penetrating cholinesterase inhibitor neostigmine also prevents or substantially inhibits those cognitive and fMRI changes. Intact cerebral blood flow and optimal metabolism are crucial for the normal functioning of neurons and other cells in the brain. Drugs that are not BBB penetrating yet act on the CNS highlight the importance of unimpaired circulation, and point to the cerebral vasculature as a primary target for drug action in diseases where impaired circulation and consequently suboptimal energy metabolism are followed by upstream pathologic events. PMID:24643080

  19. [Proposal of endogenous anticholinergic hypothesis in Alzheimer disease].

    PubMed

    Hori, Koji; Konishi, Kimiko; Akita, Ryo; Tani, Masayuki; Tomioka, Hiroi; Kitajima, Yuka; Yokoyama, Sachiko; Azuma, Kazunari; Ikuse, Daisuke; Akashi, Norinao; Yuda, Hajime; Hachisu, Mitsugu

    2013-06-01

    We previously speculated that anticholinergic activity (AA) endogenously appeared in Alzheimer's disease (AD) and accelerated AD pathology. In this article we introduce manuscripts supporting the endogenous appearance of AA in AD and the acceleration of AD pathology. We speculate that acethylcholine (ACh) not only is related to cognitive functions but also regulates the inflammatory system. Therefore in AD, in which the ACh system is down-regulated, the hyperactivity of the inflammatory system may be caused and among cyctokines, substances having anticholinergic properties may appear. We also refer to a case in which serum anticholinergic activity (SAA) disappeared with the prescription of memantine (an antidementia agent that has the property of the N-methyl-D-aspartate (NMDA) receptor blocker) and speculate that because the hyperactivity of the inflammatory system occurs by way of the hyperactivity of NMDA receptor, memantine could abolish the AA.

  20. 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

  1. 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.

  2. Acute Generalized Exanthematous Pustulosis Due to Labetalol; Drug Fever and Leukocytosis Caused by Tigecycline; Toxic Hepatitis Induced by Methylprednisolone Intravenous Pulse Dosing; Mitoxantrone-Related Osteonecrosis of the Jaw; Medications with Anticholinergic Effects and Their Implications in the Elderly.

    PubMed

    Mancano, Michael A

    2016-06-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) Med Watch program (800-FDA-1088). If you have reported an interesting, preventable ADR to Med Watch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's Med Watch program and Temple University School of Pharmacy. ISMP is an FDA Med Watch partner. PMID:27354743

  3. 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.

  4. Atropinic (Anticholinergic) Burden in Parkinson's Disease.

    PubMed

    De Germay, Sibylle; Montastruc, Jean-Louis; Rousseau, Vanessa; Chebane, Leila; Bondon-Guitton, Emmanuelle; Moulis, Florence; Durrieu, Genevieve; Bagheri, Haleh; Rascol, Olivier; Pariente, Antoine; Bégaud, Bernard; Montastruc, François

    2016-05-01

    Use of atropinic drugs remains controversial in Parkinson's disease (PD) because there is insufficient evidence about their efficacy and they can induce serious adverse drug reactions. Atropinic risk scales were developed to help to identify atropinic drugs in prescription forms and to evaluate their burden in clinical practice. In the present review, we discuss the few studies investigating atropinic burden in PD and present the results of our study indicating that atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions) with a clinically significant atropinic burden in around 1 of 6 PD patients. Drugs mainly responsible for high values of atropinic burden were those used for nonmotor symptoms. Clinically significant atropinic burdens were mainly induced by associations of several "low-risk" drugs. Physicians must be aware that in addition to classical atropinic antiparkinsonian drugs, many others (psychotropics) can contribute to increased atropinic burden in PD patients. © 2016 International Parkinson and Movement Disorder Society. PMID:27028036

  5. 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.

  6. Cognitive Decline in Older Persons Initiating Anticholinergic Medications

    PubMed Central

    Shah, Raj C.; Janos, Alicia L.; Kline, Julia E.; Yu, Lei; Leurgans, Sue E.; Wilson, Robert S.; Wei, Peter; Bennett, David A.; Heilman, Kenneth M.; Tsao, Jack W.

    2013-01-01

    Background This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. PMID:23741303

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

    PubMed

    Nagy, László Béla

    2015-08-01

    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.

  8. Amelioration of scopolamine-induced amnesia by phosphatidylserine and curcumin in the day-old chick.

    PubMed

    Barber, Teresa A; Edris, Edward M; Levinsky, Paul J; Williams, Justin M; Brouwer, Ari R; Gessay, Shawn A

    2016-09-01

    In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day-old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state-dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease. PMID:27388114

  9. Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

    PubMed

    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

    2012-01-01

    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 U 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 intra-detrusor 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 intra-detrusor 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 intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition.

  10. 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

  11. 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.

  12. 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

  13. [Drug-induced dementia].

    PubMed

    Kojima, Taro; Akishita, Masahiro

    2016-03-01

    Many drugs have been reported to induce not only delirium but also cognitive impairment. Some types of drugs are reported to induce dementia, and prolonged hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral antidiabetic drugs could result in dementia. Recently, taking multiple drugs with anticholinergic activity are reported to cause cognitive decline and anticholinergic burden should be avoided especially in patients with dementia. Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and withdrawal of the offending drug is essential to improve cognitive function. PMID:27025096

  14. 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

  15. The effects of scopolamine on three different types of suppressed behavior of rats.

    PubMed

    McKim, W A

    1980-03-01

    Twelve albino rats were trained to lever press on a variable-interval one min schedule for sweetened condensed milk reinforcement. While responding on this schedule a two minute tone was presented. For one group it signalled a response contingent shock (Punishment), for another group it signalled the delivery of an unavoidable non-contingent shock at its termination (CER) and for a third group, reinforcement was withheld during the tone (Extinction). In the first experiment scopolamine in doses of 0.8 to 12.8 mg/kg did not alter response rates during the tone for any group. In a second experiment 16 hooded rats were tested with 6.4 mg/kg of scopolamine using a similar procedure, but with different shock levels, apparatus, reinforcement and session duration. For all three groups the drug depressed responding during the tone. It was concluded that when all other aspects of the situation are equated scopolamine will produce the same effect on behavior suppressed by punishment, CER and extinction. PMID:7393939

  16. 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.

  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. PMID:22475379

  18. Anticholinergic action of pirenzepine (Gastrozepin) on isolated gastrointestinal tract smooth muscles.

    PubMed

    Ojewole, J A

    1983-01-01

    The effects of pirenzepine, a new anti-ulcer drug, have been examined on acetylcholine (ACh)-induced contractions of the guinea-pig isolated ileum, rat colon, rainbow lizard rectum, and chick isolated oesophagus. Pirenzepine (10(-9)-10(-6) M), like atropine (2.5 x 10(-10)-10(-6) M) competitively blocked the contractile effects of acetylcholine on all the isolated gastrointestinal tract smooth muscles examined. The pA2 values for pirenzepine and atropine against acetylcholine on all the muscle preparations were not significantly different (P greater than 0.05). It is concluded that the anti-ulcer action of pirenzepine might be due, at least in part, to its (anticholinergic) muscarinic cholinoceptor blocking activity.

  19. 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.

  20. 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. PMID:25953832

  1. 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

  2. Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je

    2016-01-01

    Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer’s disease. PMID:27133261

  3. Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice.

    PubMed

    Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je

    2016-05-01

    Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.

  4. The use of a scopolamine model to study the potential nootropic effects of aniracetam and piracetam in healthy volunteers.

    PubMed

    Wesnes, K; Anand, R; Simpson, P; Christmas, L

    1990-01-01

    In this study 26 healthy volunteers received scopolamine 0.7 mg subcutaneously on seven occasions at least a week apart. Cognitive efficiency was measured with a test battery before and 60 min following scopolamine on each occasion. Following this, over the seven occasions, a range of oral and intravenous dose regimens were administered including aniracetam 2 mg intravenously, 100 mg intravenously, 200 mg intravenously, 1500 mg per os and piracetam 2400 mg per os. On each session the test battery was then performed again at 120 and 200 min following scopolamine. The seven treatments were administered double- blind and the order was counterbalanced between volunteers over visits using a Latin Square design. At 60 min, scopolamine produced marked and significant decrements in all of the measures of memory and information processing. Aniracetam 1500 mg was able to sig nificantly antagonize decrements on both memory and information processing tasks. The other active treatments also produced significant effects, but for two these were equal to, and for two slightly above, the number which may have occurred by chance, and thus were questionable. Overall, the findings demonstrate that aniracetam 1500 mg can antagonize cognitive decrements produced by cholinergic blockade in healthy volunteers, and suggest that the drug possesses nootropic properties.

  5. 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. PMID:16719539

  6. Biotransformation of hyoscyamine into scopolamine in transgenic tobacco cell cultures.

    PubMed

    Moyano, Elisabeth; Palazón, Javier; Bonfill, Mercedes; Osuna, Lidia; Cusidó, Rosa M; Oksman-Caldentey, Kirsi-Marja; Piñol, M Teresa

    2007-04-01

    Hyoscyamine-6beta-hydroxylase (H6H) catalyses the conversion of hyoscyamine into its epoxide scopolamine, a compound with a higher added value in the pharmaceutical market than hyoscyamine. We report the establishment of tobacco cell cultures carrying the Hyoscyamus muticus h6h gene under the control of the promoter CAMV 35S. The cell cultures were derived from hairy roots obtained via genetically modified Agrobacterium rhizogenes carrying the pRi and pLAL21 plasmids. The cultures were fed with hyoscyamine, and 4 weeks later the amount of scopolamine produced was quantified by HPLC. The transgenic cell suspension cultures showed a considerable capacity for the bioconversion of hyoscyamine into scopolamine, and released it to the culture medium. Although the scale-up from shake-flask to bioreactor culture usually results in reduced productivities, our transgenic cells grown in a 5-L turbine stirred tank reactor in a batch mode significantly increased the scopolamine accumulation.

  7. Synergism of theophylline and anticholinergics to inhibit haloperidol-induced catalepsy: a potential treatment for extrapyramidal syndromes.

    PubMed

    González-Lugo, Olga E; Ceballos-Huerta, Fátima; Jiménez-Capdeville, María E; Arankowsky-Sandoval, Gloria; Góngora-Alfaro, José L

    2010-12-01

    Extrapyramidal syndromes (EPS) impose a heavy burden on patients receiving antipsychotic therapy. Anticholinergics are the drugs of choice for preventing EPS, but they also produce many adverse reactions. Using the EPS model of haloperidol-induced catalepsy we evaluated the potential therapeutic value of a mixture of low doses of the non-selective adenosine antagonist theophylline (0.93 and 1.86 mg/kg), and the muscarinic antagonists benztropine (0.134 and 0.268 mg/kg) and ethopropazine (0.116 and 0.232 mg/kg). In rats pretreated with vehicle (distilled water), the cumulative catalepsy time over 5 h was 4199±228 s, and the mean latency was 67.5±7.8 min. Applied separately, neither of the drugs at the doses used caused significant changes of catalepsy intensity vs. control rats. However, the combination of the larger doses of theophylline and benztropine caused a significant reduction of catalepsy intensity (-41±10%) compared with the effects of the vehicle, vs. the lower dose of benztropine, and vs. both doses of theophylline alone. The mixture of the larger doses of theophylline and benztropine also delayed catalepsy onset (156±21 min) as compared with the lower doses of these same drugs applied alone. In the case of theophylline plus ethopropazine, only the association of the larger doses showed a non-significant tendency to inhibit catalepsy (-21±8%) and to prolong its latency (108±13 min). Further, neither catalepsy intensity nor its latency was affected by a combination of the selective A(1)R antagonist DPCPX (1 mg/kg), with the larger doses of both anticholinergics. In contrast, the anticholinergics showed synergism with a subthreshold dose of the selective A(2A)R antagonist ZM 241395 (0.5 mg/kg), causing a significant reduction of catalepsy intensity (ethopropazine, -27±5%; benztropine, -35±9%) and prolonging its latency (ethopropazine, 65±9 min; benztropine, 78±11 min), compared with the effect of their respective vehicle (DMSO plus mineral oil

  8. Demonstrating the Role of Anticholinergic Activity in a Mood Disorder.

    PubMed

    Hori, Koji; Konishi, Kimiko; Hanashi, Takahiro; Tani, Masayuki; Tomioka, Hiroi; Kitajima, Yuka; Akashi, Norihisa; Inamoto, Atsuko; Kurosawa, Kenzo; Hasegawa, Sayaka; Izuno, Takuji; Kikuchi, Nodoka; Hosoi, Misa; Hachisu, Mitsugu

    2015-01-01

    We report a case of a 54-year-old woman presenting with amnesia, apathy, work-related difficulties and mental stress. At presentation, her Mini-Mental State Examination score was 27 and her serum anticholinergic activity (SAA) was positive without medication or recent physical illnesses. In addition, magnetic resonance imaging revealed mild atrophy of the frontal and temporal lobes, with a relatively intact hippocampus. Consequently, we diagnosed mild cognitive impairment due to Alzheimer's disease and prescribed a cholinesterase inhibitor (donepezil, 10 mg/day); her SAA fully disappeared and clinical symptoms partially resolved. Addition of duloxetine coupled with environmental adjustments caused her cognitive function to return to a normal level, so we diagnosed pseudodementia due to depression. In this case, we believe that the simultaneous cholinergic burden and mental stress led to positive SAA, which made it reasonable to prescribe a cholinesterase inhibitor to ameliorate the associated acetylcholine hypoactivity. We believe that it is essential to recognize the importance of prescribing a cholinesterase inhibitor for specific patients, even those with pseudodementia, to control their clinical symptoms. Moreover, SAA might be a useful biomarker for identifying this subgroup of patients. We propose that anticholinergic activity appears endogenously in mood disorders (depression and bipolar disorder) and set out our rationalization for this hypothesis. PMID:26138496

  9. 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.

  10. 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

  11. 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.

  12. 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. PMID:24823431

  13. 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.

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

    PubMed

    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

  15. 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

  16. Choline reverses scopolamine-induced memory impairment by improving memory reconsolidation.

    PubMed

    Blake, M G; Boccia, M M; Krawczyk, M C; Delorenzi, A; Baratti, C M

    2012-09-01

    It is widely known that pre-training systemic administration of the muscarinic antagonist scopolamine (SCP) (0.5mg/kg, i.p.) leads to anterograde memory impairment in retention tests. The administration of the α(7)-nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8μg/hippocampus) immediately after memory reactivation allowed recovery from scopolamine-induced memory impairment. This effect of Ch was time-dependent, and retention performance was not affected in drug-treated mice that were not subjected to memory reactivation, suggesting that the performance effects are not due to non-specific effects of the drug. The effects of Ch also depended on the age of the reactivated memory. Altogether, our results suggest that Ch exerts its effects by modulating memory reconsolidation, and that the memory impairment induced by low doses of SCP is a memory expression failure and not a storage deficit. Therefore, reconsolidation, among other functions, might serve to change memory expression in later tests. Summarizing, our results open new avenues about the behavioral significance and the physiological functions of memory reconsolidation, providing new strategies for recovering memories from some types of amnesia.

  17. Anxiolytic effects of environmental enrichment attenuate sex-related anxiogenic effects of scopolamine in rats.

    PubMed

    Hughes, Robert N; Otto, Maria T

    2013-01-10

    In groups of four same-sexed animals, PVG/c hooded rats were housed for 4.5 months in standard or enriched cages containing several objects that could be explored and manipulated. On separate occasions, each rat then experienced two consecutive daily trials in an open field, a light-dark box or a Y maze with arm inserts that enabled an acquisition trial comprising one black and one white arm to be changed for a retention trial consisting of two black arms. Before their trials in the open field and light-dark box, and following each acquisition trial in the Y maze, the rats received an intraperitoneal injection of 2 mg/kg scopolamine or isotonic saline. In the open field, enrichment led to higher levels of ambulation, walking, rearing and occupancy of the center of the apparatus and shorter emergence latencies from the dark into the light compartment of the light-dark box accompanied by more entries of this compartment. Enrichment also increased entries of and time spent in the changed (or novel) Y-maze arm only for male rats treated with scopolamine. The drug decreased rearing and increased grooming in the open field as well as increasing emergence latencies and decreasing entries of and the time spent on the light compartment of the light-dark box. The main results were interpreted as enrichment having attenuated anxiogenic effects of the behavioral testing and the action of scopolamine for male (but not female) rats in their choices of the novel arm in the Y maze.

  18. 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.

  19. 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.

  20. Suspected Central Anticholinergic Syndrome Related to Cycloplegic Eye Drop in a Premature Baby

    PubMed Central

    Bedirli, Nurdan; Akgün, Fatma; Hondur, Ahmet; Işık, Berrin

    2012-01-01

    The therapeutic approach for the central anticholinergic syndrome after application of cycloplegic eye drops in a premature infant patient who was scheduled for laser photocoagulation under general anesthesia is reviewed in the light of the relevant literature. PMID:25207025

  1. Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic acetylcholine receptor occupancies.

    PubMed

    Haraguchi, K; Ito, K; Kotaki, H; Sawada, Y; Iga, T

    1997-06-01

    It is known that catalepsy serves as an experimental animal model of parkinsonism. In this study, the relationship between in vivo dopamine D1 and D2 receptor occupancies and catalepsy was investigated to predict the intensity of catalepsy induced by drugs that bind to D1 and D2 receptors nonselectively. 3H-SCH23390 and 3H-raclopride were used for the labeling of D1 and D2 receptors, respectively. The ternary complex model consisting of agonist or antagonist, receptor, and transducer was developed, and the dynamic parameters were determined. After coadministration of SCH23390 and nemonapride, catalepsy was stronger than sum of the values predicted by single administration of each drug, and it was intensified synergistically. This finding suggested the existence of interaction between D1 and D2 receptors, and the necessity for constructing the model including this interaction. To examine the validity of this model, catalepsy and in vivo dopamine receptor occupancy were measured after administration of drugs that induce or have a possibility to induce parkinsonism (haloperidol, flunarizine, manidipine, oxatomide, hydroxyzine, meclizine, and homochlorcycilzine). All of the tested drugs blocked both dopamine D1 and D2 receptors. Intensity of catalepsy was predicted with this dynamic model and was compared with the observed values. In contrast with haloperidol, flunarizine, manidipine, and oxatomide (which induced catalepsy), hydroxyzine, meclizine, and homochlorcyclizine failed to induce catalepsy. Intensities of catalepsy predicted with this dynamic model considering the interaction between D1 and D2 receptors overestimated the observed values, suggesting that these drugs have catalepsy-reducing properties as well. Because muscarinic acetylcholine (mACh) receptor antagonists inhibit the induction of catalepsy, the anticholinergic activities of the drugs were investigated. After SCH23390, nemonapride and scopolamine were administered simultaneously; catalepsy and in

  2. 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.

  3. 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

  4. Scopolamine-induced convulsions in fasted mice after food intake: the effect of duration of food deprivation.

    PubMed

    Enginar, Nurhan; Nurten, Asiye; Ozünal, Zeynep Güneş; Zengin, Asli

    2009-01-01

    It has been shown that mice and rats treated with antimuscarinic drugs, scopolamine or atropine, after fasting for 48 h develop convulsions soon after refeeding. The present study was performed to evaluate whether mice also develop convulsions after being deprived of food for 1-24 h. The effect of day-night fasting on the development of convulsions was also determined in 12-h deprived animals. Mice were deprived of food for periods of 1, 2, 3, 6, 9, 12, 18, 24, and 48 h. Animals fasted for 12 h during the day or night were deprived of food at 08:00 or 20:00 h, respectively. At the time of testing, animals were treated with intraperitoneal (i.p.) saline or 3 mg/kg scopolamine. Twenty minutes later, they were given food and allowed to eat ad lib. All animals were observed for 30 min for the incidence and onset of convulsions. Fasted animals treated with scopolamine developed clonic convulsions after food intake. Incidence of convulsions was significant in 2-, 3-, 12-, 18-, 24-, and 48-h deprived animals. Convulsions observed after deprivation of food for 12 h during the day or at night were almost similar in both regimens. Our results indicate that food deprivation itself, rather than its duration, seems to be the principal factor in the development of these convulsions.

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

    PubMed

    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 5(th) 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

  6. Use of anticholinergics and the risk of cognitive impairment in an African American population

    PubMed Central

    Campbell, N.L.; Boustani, M.A.; Lane, K.A.; Gao, S.; Hendrie, H.; Khan, B.A.; Murrell, J.R.; Unverzagt, F.W.; Hake, A.; Smith-Gamble, V.; Hall, K.

    2010-01-01

    Background: Anticholinergic properties of certain medications often go unrecognized, and are frequently used by the elderly population. Few studies have yet defined the long-term impact of these medications on the incidence of cognitive impairment. Methods: We report a 6-year longitudinal, observational study, evaluating 1,652 community-dwelling African American subjects over the age of 70 years who were enrolled in the Indianapolis-Ibadan Dementia Project between 2001 and 2007 and who had normal cognitive function at baseline. The exposure group included those who reported the baseline use of possible or definite anticholinergics as determined by the Anticholinergic Cognitive Burden scale. Our main outcome measure was the incidence of cognitive impairment, defined as either dementia or cognitive impairment not dementia, or poor performance on a dementia screening instrument during the follow-up period. Results: At baseline, 53% of the population used a possible anticholinergic, and 11% used a definite anticholinergic. After adjusting for age, gender, educational level, and baseline cognitive performance, the number of definite anticholinergics was associated with an increased risk of cognitive impairment (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.07–1.99; p = 0.02), whereas the number of possible anticholinergics at baseline did not increase the risk (OR 0.96, 95% CI 0.85–1.09; p = 0.55). The risk of cognitive impairment among definite anticholinergic users was increased if they were not carriers of the APOE ε4 allele (OR 1.77, 95% CI 1.03–3.05; p = 0.04). Conclusions: Limiting the clinical use of definite anticholinergics may reduce the incidence of cognitive impairment among African Americans. GLOSSARY ACB = Anticholinergic Cognitive Burden scale; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; CI = confidence interval; CIND = cognitive impairment no dementia; CSI-D = Community Screening Interview for Dementia; DSM

  7. 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.

  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. Bilateral skin conductance and the pupillary light-dark reflex: manipulation by chlorpromazine, haloperidol, scopolamine, and placebo.

    PubMed

    Patterson, T; Venables, P H

    1981-01-01

    Cholinergic blocking with scopolamine produces skin conductance orientating response (SCOR) nonresponding in normal subjects. This may be one of a number of causes for nonresponding in schizophrenic subjects. Blockade of dopamine with haloperidol produces an increase in amplitude and shortening of recovery time in the SCOR of normal subjects. This result closely resembles that of Nielsen and Petersen (1976) who found a similar pattern of responding in normal subjects who scored high on a scale of schizophrenism. These results, along with those for chlorpromazine and the pupillographic effects of the three drugs are discussed in terms of biochemical working hypotheses of schizophrenic subclassification.

  10. Different behavior toward muscarinic receptor binding between quaternary anticholinergics and their tertiary analogues.

    PubMed

    Ensing, K; de Zeeuw, R A

    1986-12-01

    A number of corresponding tertiary and quaternary anticholinergic analogues were examined for their ability to inhibit specific (3)H-dexetimide binding to calf brain muscarinic receptors. In all cases the tertiary antagonists (except pirenzepine) showed steep and monophasic inhibition curves, whereas those of the quaternary derivatives were shallow (thiazinamium, methylbenactyzine) or even biphasic (oxyphenonium, methylatropine, methylscopolamine). These observations show that the addition of a methyl group to the nitrogen atom changes the mode of interaction of the anticholinergics to muscarinic receptor binding sites. Whether there are separate binding sites present or differences in interaction mode for only the quaternary moiety is discussed. PMID:24271831

  11. 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.

  12. 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. PMID:27019963

  13. Synthesis of anticholinergic agents: N-methyl-4-piperidinyl alpha-benzoyloxy-alpha-cyclopentylphenylacetate salts.

    PubMed

    Oroshnik, W; Soldati, G

    1978-05-01

    The synthesis of a new anticholinergic agent, N-methyl-4-piperidinyl alpha-benzoyloxy-alpha-cyclopentylphenylacetate, obtained by reacting N-methyl-4-piperidinyl alpha-cyclopentylmandelate with benzoyl chloride in the presence of methyllithium, is reported. This material may be useful as an antiperspirant.

  14. Muscarinic antagonists in the treatment of acquired pendular and downbeat nystagmus: a double-blind, randomized trial of three intravenous drugs.

    PubMed

    Barton, J J; Huaman, A G; Sharpe, J A

    1994-03-01

    We performed a double-blind, randomized trial of intravenous scopolamine, benztropine, and glycopyrrolate in 7 patients with acquired nystagmus and oscillopsia. Five patients had pendular nystagmus and 2, downbeat nystagmus. We recorded eye movements with a magnetic search coil technique and tested visual acuity and motion perception before and after administration of each drug. Scopolamine reduced nystagmus in all patients. Benztropine was moderately effective and glycopyrrolate had a negligible impact. Visual acuity improved only with scopolamine; motion discrimination and oscillopsia improved significantly with scopolamine and benztropine. Pendular and downbeat nystagmus respond to intravenous antagonists of central muscarinic receptors.

  15. The effects of different types of pre-training on the rat's retention performance in a swim-to-platform task following administration of scopolamine.

    PubMed

    Caldji, C; Vanderwolf, C H

    1996-10-01

    Previous research has found that centrally acting antimuscarinic drugs strongly impair the acquisition of a variety of learned behaviors in rats but have little effect on these same behaviors if training is given prior to drug treatment. We gave groups of rats different types of pre-training followed by treatment with scopolamine hydrobromide and subsequent testing on a simple swim-to-platform test. Factors such as practice in swimming without a platform to escape to, or learning to swim to a platform in a different apparatus or even to the test platform located in a different place did not protect the rats from the behavioral disruption produced by scopolamine. However, five training trials on the specific swim-to-platform task used in the retention test afforded almost complete protection against the effect of scopolamine. It appears that the protective effect of pre-training is highly specific and does not involve acquisition of some type of general rule which might survive antimuscarinic blockade.

  16. 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.

  17. 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

  18. 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.

  19. Alpha7 nicotinic acetylcholine receptor activation ameliorates scopolamine-induced behavioural changes in a modified continuous Y-maze task in mice.

    PubMed

    Redrobe, John P; Nielsen, Elsebet Ø; Christensen, Jeppe K; Peters, Dan; Timmermann, Daniel B; Olsen, Gunnar M

    2009-01-01

    The alpha7 (alpha7) nicotinic acetylcholine receptor may represent a drug target for the treatment of disorders associated with working memory/attentional dysfunction. We investigated the effects of three distinct alpha7 nicotinic acetylcholine receptor agonists: 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941; 0.01-0.1 mg/kg), 4-bromophenyl 1,4-diazabicyclo(3.2.2) nonane-4-carboxylate (SSR180711; 0.3-3 mg/kg) and N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide (PNU-282987; 1-10 mg/kg), on scopolamine-induced deficits in a modified Y-maze procedure. Mice were forced to choose one of two visually distinct arms, and were confined there for a 5 min exploration period before being allowed to explore both arms for a 2 min test session, immediately thereafter. The time spent in each arm, entries and total distance travelled were recorded using an automated system. Characterisation experiments showed that scopolamine-treated (1 mg/kg) mice spent less time exploring the unfamiliar arm, when compared with vehicle-treated animals. Combination experiments showed that all three alpha7 agonists ameliorated scopolamine-induced changes in unfamiliar arm exploration. In conclusion, the present data support the idea that alpha7 nicotinic acetylcholine receptors may represent an interesting target for the treatment of conditions associated with attentional/working memory dysfunction.

  20. 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. PMID:27443047

  1. 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. PMID:26366965

  2. Anticholinergic syndrome due to 'Devil's herb': when risks come from the ancient time.

    PubMed

    Piccillo, G A; Miele, L; Mondati, E; Moro, P A; Musco, A; Forgione, A; Gasbarrini, G; Grieco, A

    2006-04-01

    We describe a case of Mandragora autumnalis poisoning which occurred in a 72-year-old female patient who had eaten the venenous M. Autumnalis, picked near her home, mistaking it for the edible Borago Officinalis. M. Autumnalis is a solanaceous plant, common in the Sicilian countryside, which contains a variable concentration of solanum alkaloids, causing gastrointestinal irritation, and tropane alkaloids, with anticholinergic properties. Unluckily, M. Autumnalis is often mistaken for the edible B. Officinalis, likewise widespread in Sicilian countryside. The diagnosis of Mandragora poisoning was made on the basis of clinical symptoms and signs of anticholinergic syndrome associated with a history of vegetable meal of uncontrolled origin, moreover analysing the vegetable obtained from gastric lavage. Decontamination and symptomatic treatment were useful in our patient to control acute poisoning. PMID:16620365

  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. 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.

  5. A study of the need for anticholinergic medication in patients treated with long-term antipsychotics.

    PubMed

    Caradoc-Davies, G; Menkes, D B; Clarkson, H O; Mullen, P E

    1986-06-01

    Studies on the withdrawal of anticholinergics from patients on antipsychotics have produced conflicting results. This 12-week study employed a double-blind crossover design on 39 adult in-patients selected from a total hospital population of 620. The Colombia Scale was used to determine extrapyramidal side effects (EPS). All patients were stabilised prior to the study on benztropine mesylate 2 mg b.i.d., and gradual withdrawal was employed. Benztropine withdrawal produced a significant increase in overall EPS scores. Ten patients (26%) required reinstatement of benztropine while on placebo. Sialorrhoea, rigidity and postural instability were the most prominent changes. Neither age, sex, nor diagnosis were significantly predictive of EPS. Depot medications and doses greater than 1000 mg/day chlorpromazine-equivalent were related to significant EPS increase. The intrinsic anticholinergic properties of the antipsychotics themselves and concomitant medications, such as antidepressants, appeared protective against development of EPS. Most patients on a combination of antipsychotics and anticholinergics can safely be withdrawn from the latter.

  6. Clinical Efficacy in the Treatment of Overactive Bladder Refractory to Anticholinergics by Posterior Tibial Nerve Stimulation

    PubMed Central

    Palao-Yago, Francisco; Campon-Pacheco, Iluminada; Martinez-Sanchez, Maribel; Zuluaga-Gomez, Armando; Arrabal-Martin, Miguel

    2012-01-01

    Purpose Overactive bladder (OAB) is a clinical syndrome that is currently treated initially with anticholinergics, although some other therapeutic alternatives exist, such as neuromodulation, botulinum toxin, and posterior tibial nerve stimulation (PTNS). The purpose of this study was to assess the efficacy of PTNS in patients with OAB refractory to anticholinergics. Materials and Methods We present a cohort study of 14 women with OAB to whom we applied PTNS. We assessed (before and after the treatment) the diurnal micturitional frequency, the nocturnal micturitional frequency, urgency episodes, and urge incontinence episodes. Results were analyzed by using the Wilcoxon test for nonparametric samples. Results We observed statistically significant improvement in the diurnal micturitional frequency (p=0.05), in episodes of micturitional urgency (p=0.03), and in episodes of urge incontinence (p=0.004). A total of 50% of the patients felt subjective improvement from their pathology. Conclusions PTNS is a valid, minimally invasive treatment option with minimum morbidity for patients with OAB refractory to treatment with anticholinergics. PMID:22866220

  7. 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

    ...-2004/0-DE-07]; 4. French Patent 1896025, issued December 28, 2011, titled ``Scopolamine for the Treatment of Depression and Anxiety'' [HHS Ref. No. E-175-2004/0-FR-08]; 5. British Patent 1896025,...

  8. 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

    2014-08-01

    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

  9. Comparative protective action of curcumin, memantine and diclofenac against scopolamine-induced memory dysfunction.

    PubMed

    Ali, Elham H A; Arafa, Nadia M S

    2011-06-01

    The comparative preventive effect of curcumin, memantine, and diclofenac on scopolamine-induced memory dysfunction was investigated in a controlled study. A group of male and female rats was treated with one of these compounds for 15 days, after which a single dosage of scopolamine was administered. The preventive activity of curcumin on memory dysfunction was higher than that of diclofenac or memantine, that was, however, administered at lower dosages. Gender differences were observed.

  10. Scopolamine and acquisition of go-no go avoidance: a further analysis of the perseverative antimuscarinic deficit.

    PubMed

    Giardini, V; Amorico, L; De Acetis, L; Bignami, G

    1983-01-01

    Rats treated with scopolamine (0.5 mg/kg SC daily) during the acquisition of a discrimination task with symmetrical negative reinforcement (light-go, noise/light-no go) showed a learning impairment, with both active and passive avoidance deficits. In the initial stage of such training, however, fewer passive avoidance errors and more active avoidance errors were made by treated animals if active avoidance pretraining had occurred in the no-drug state. A similar experiment using the same stimulus arrangement with asymmetrical reinforcement (no punishment of intertrial, and no go signal, responses) showed a scopolamine effect consisting mainly of increased responding to extinction signals and during intertrial intervals, with little or no active avoidance deficit. Furthermore, interactions due to changes in treatment conditions in successive stages of training were minimized in the latter task, suggesting that the effects of the shift-no shift factor on distribution of errors in the early stages of active-passive avoidance learning were unlikely to have been due to a genuine drug dissociation. Overall, these results and others obtained previously in the same and related tasks tend to rule out some unidimensional explanations of antimuscarinic effects, e.g., response disinhibition (an exclusively motor deficit) or impairment of stimulus sensitivity (an exclusively sensory deficit). The data rather confirm the notion of a sensorimotor drug bias leading to a shift in response prepotencies depending jointly on stimuli, responses, and response consequences. Prior learning history and behavioural compensation for adverse treatment consequences at the reinforcement level may interact with the sensorimotor bias so as to produce "set perseveration" (perseveration of response tendencies). PMID:6410441

  11. 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. PMID:24938777

  12. Ginsenoside Rh2 ameliorates scopolamine-induced learning deficit in mice.

    PubMed

    Yang, Jung-Hwa; Han, Sang-Jun; Ryu, Jong Hoon; Jang, Il-Sung; Kim, Dong-Hyun

    2009-10-01

    To understand memory-enhancing effect of red ginseng biotransformed by Bifidobacterium longum H-1 (RGB), which more potently improved scopolamine-induced learning deficit than red ginseng in the preliminary experiment, its main constituents, ginsenosides Rb1, Rg3 and Rh2, were isolated and their memory-enhancing effects investigated in scopolamine-treated mice by using passive avoidance and Y-maze tests. Among them, ginsenoside Rh2 most potently reversed memory impairment caused by scopolamine. Ginsenoside Rh2 also significantly shortened the escape latencies prolonged by scopolamine in the Morris water maze test (p<0.001) and increased the swimming time shorten by scopolamine within the platform quadrant (p<0.05). The ginsenoside Rh2 (3 muM) reversed scopolamine (10 muM)-induced suppression of long-term potentiation. It recovered field excitatory post synaptic potential (fEPSP) amplitude potentiation to 152.3+/-8.7% of the control (p<0.05). Based on these findings, RGB and its main constituent, ginsenoside Rh2, might improve learning deficits. Also the memory-enhancing effects of RGB may be dependent on the content of ginsenoside Rh2.

  13. Functional antidopaminergic and anticholinergic effects of thioridazine and its metabolites

    SciTech Connect

    Niedzwiecki, D.

    1986-01-01

    The relative potency of thioridazine and two of its clinically active metabolites, mesoridazine and sulforidazine was studied. In each of three separate methods, mesoridazine and sulforidazine exhibited greater potency than did thioridazine. Both metabolites showed greater affinities for striatal DA receptors as estimated by their competition for (/sup 3/H)spiperone binding sites in crude striatal membrane preparations. On a more functional level, both metabolites more potently antagonized the inhibitory effects of either the direct acting DA agonist apomorphine, or of endogenous DA, on the electrically evoked release of radiolabeled DA and ACh from perfused striatal slices. While thioridazine effectively blocked the agonist-induced inhibition at those striatal DA receptors which control DA release, it showed significantly lower potency at the striatal DA receptors which modulate ACh release. Thioridazine exhibited moderate affinity for striatal muscarinic cholinergic receptors. It was only five times less potent than atropine in competing for (/sup 3/H) quinuclidinylbenzilate binding sites in striatal membrane preparations. Unlike dopamine receptors, thioridazine showed greater antimuscarinic potency than did its metabolites. Despite this significant affinity for muscarinic binding sites in striatal homogenates, neither thioridezine nor its metabolites could block the inhibitory effects of the full muscarinic agonist carbachol, on the evoked release of ACh from striatal slices. This lack of effect contrasted with the antagonism of the carbachol-induced inhibition by such classical muscarinic blockers as quinuclindinylbenzilate or atropine. In combination with available pharmacokinetic data, these studies have demonstrated that the metabolites of thioridazine probably contribute to the antidopaminergic effects of this drug within the CNS.

  14. Inhaled adrenergics and anticholinergics in obstructive lung disease: do they enhance mucociliary clearance?

    PubMed

    Restrepo, Ruben D

    2007-09-01

    Pulmonary mucociliary clearance is an essential defense mechanism against bacteria and particulate matter. Mucociliary dysfunction is an important feature of obstructive lung diseases such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, and bronchiectasis. This dysfunction in airway clearance is associated with accelerated loss of lung function in patients with obstructive lung disease. The involvement of the cholinergic and adrenergic neural pathways in the pathophysiology of mucus hypersecretion suggests the potential therapeutic role of bronchodilators as mucoactive agents. Although anticholinergics and adrenergic agonist bronchodilators have been routinely used, alone or in combination, to enhance mucociliary clearance in patients with obstructive lung disease, the existing evidence does not consistently show clinical effectiveness.

  15. [Neurological complications following anesthesia--part I. Perioperative stroke, postoperative visual loss, anticholinergic syndrome].

    PubMed

    Adam, Christian; Quabach, Ralf; Standl, Thomas

    2010-07-01

    Neurological complications following anesthesia deteriorate patients' outcome, and increase hospital costs because of prolonged hospitalization and supplemental medical care. Moreover, patients' satisfaction is negatively influenced by neurological sequelae after anesthesia. Improving anesthesiologic management based on consequent prevention measures can help to reduce the incidence of neurological complications after anesthesia. In case of neurological complications in the perioperative phase an interdisciplinary approach in immediate diagnosis and treatment may prevent patients from permanent damage. The present review article gives an overview over incidences, diagnostic and therapeutic issues of neurologic complications in operative patients, such as perioperative stroke, postoperative visual loss and the anticholinergic syndrome. PMID:20665352

  16. 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. PMID:25546299

  17. 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.

  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. 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

  20. 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

  1. 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.

  2. Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset.

    PubMed

    Carey, G J; Costall, B; Domeney, A M; Gerrard, P A; Jones, D N; Naylor, R J; Tyers, M B

    1992-05-01

    The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive impairment induced by the muscarinic receptor antagonist, scopolamine. For this purpose, marmosets were trained in an object discrimination task utilizing the Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg, SC) caused a dose-dependent impairment in the acquisition of the object discrimination task in that marmosets required more trials to reach criterion, made more errors, and took longer to choose the objects. Administration of arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1 micrograms/kg, SC) prevented the scopolamine-induced impairment in task acquisition in that the performance of marmosets was indistinguishable from that of saline-treated animals and was significantly better than that following scopolamine/saline. From these studies, we conclude that ondansetron prevents impairment in the cognitive performance of marmosets induced by administration of scopolamine.

  3. 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

  4. 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

  5. Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats.

    PubMed

    Heo, Yu-Mi; Shin, Mal-Soon; Kim, Su-Hyun; Kim, Tae-Wook; Baek, Sang-Bin; Baek, Seung-Soo

    2014-06-01

    Alzheimer's disease is the most common neurodegenerative disease and this disease induces progressive loss of memory function Scopolamine is a non-selective muscarinic cholinergic receptor antagonist and it induces impairment of learning ability. Exercise is known to ameliorate memory deficits induced by various brain diseases. In the present study, we investigated the effect of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus using the scopolamine-induced amnesia mice. For the induction of amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once a day for 14 days. Morris water maze test for spatial learning ability was conducted. Immonofluorescence for 5-bromo-2-deoxyuri-dine (BrdU) and western blot for brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) were performed. In the present results, scopolamine-induced amnesia mice showed deterioration of spatial learning ability. Inhibition of cell proliferation and suppression of BDNF and TrkB expressions were observed in the scopolamine-induced amnesia mice. Treadmill exercise improved spatial learning ability and increased cell proliferation through activating of BDNF-TrkB pathway in the amnesia mice. These findings offer a possibility that treadmill exercise may provide preventive or therapeutic value for the memory loss induced by variable neurodegenerative diseases including Alzheimer's disease.

  6. 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. PMID:25121635

  7. Phoenixin-14 enhances memory and mitigates memory impairment induced by Aβ1-42 and scopolamine in mice.

    PubMed

    Jiang, J H; He, Z; Peng, Y L; Jin, W D; Wang, Z; Mu, L Y; Chang, M; Wang, R

    2015-12-10

    Phoenixin (PNX) is a recently discovered neuropeptide shown to be involved in regulating the reproductive system, anxiety-related behaviors and pain though its receptor is still unknown. PNX-14, one of the endogenous active isoforms, is reported to regulate gonadotropin releasing hormone (GnRH) receptor expression and GnRH secretion. Because GnRH system is thought to be involved in the regulation of learning and memory processes, we hypothesized that PNX-14 might be mediate learning and memory. Here, we investigated the effects of PNX-14 in memory processes, using novel object recognition (NOR) and object location recognition (OLR) tasks. Our results revealed that intracerebroventricular (i.c.v.) injection of PNX-14 (25nmol) immediately after training not only facilitated memory formation, but also prolonged memory retention in both tasks. The memory-enhancing effects of PNX-14 were also seen when it was infused into the hippocampus. Moreover, these memory-improving effects of PNX-14 could be blocked by a GnRH receptor antagonist (Cetrorelix). The memory-improving effects of PNX-14 were not related to any effects on locomotor activity. Additionally, the results suggested that i.c.v. injection of PNX-14 mitigate the memory impairment induced by the amyloid-β1-42 (Aβ1-42) peptide and scopolamine. The present results indicate that PNX-14 facilitates memory formation and prolongs memory retention through activation of the GnRH receptor, and mitigates the memory-impairing effects of Aβ1-42 and scopolamine, suggesting that PNX-14 may be effective as a drug for enhancing memory and treating Alzheimer׳s disease.

  8. Cisapride

    MedlinePlus

    ... medications you are taking, especially antianxiety medications, anticholinergics (atropine, belladonna, benztropine, dicyclomine, diphenhydramine, isopropamide, procyclidine, and scopolamine), ...

  9. Scopolamine prevents retrograde memory interference between two different learning tasks.

    PubMed

    Blake, M G; Boccia, M M; Krawczyk, M C; Baratti, C M

    2011-03-01

    Subjects exposed to learning experiences could store the new information through memory consolidation process. If consolidation is interfered by exposing the experimental subjects to another novel stimulus, memory of the first learning situation is sometimes disrupted. The cholinergic system is critically involved in acquisition of new information. Here, we use low doses of the muscarinic cholinergic receptor antagonist scopolamine (SCOP) to disrupt acquisition of new information, but sparing memory consolidation of previous memories. Mice were consecutively exposed to two learning situations: the inhibitory avoidance (IA) and the nose-poke habituation (NPH) tasks. The exposure of mice to the NPH task, after being trained in the IA apparatus, impairs consolidation of the avoidance memory in a manner related to the duration of the exposure to the NPH task. If the exposure to the NPH task occurred after reactivation of the avoidance memory, reconsolidation was impaired. Blockade of acquisition of the NPH task by SCOP allowed consolidation and reconsolidation of the avoidance memory. Results indicate that cholinergic system blockade by SCOP impairs acquisition but is less able to affect memory consolidation. The mere exposure and perception of a novel situation are not sufficient conditions to cause impairment of retention performance about previously learned information, but effective processing leading to acquisition of the NPH task information is necessary to cause the interference between both learning situations.

  10. 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

  11. Transderm scopolamine efficacy related to time of application prior to the onset of motion.

    PubMed

    Levy, G D; Rapaport, M H

    1985-06-01

    We evaluated Transdermal Scopolamine related to the time of application prior to the onset of motion. In this study 44 subjects participated. The first group applied the transdermal disc within 4 h and the second group 8 h or more prior to the onset of motion. We observed a significant decrease in the incidence and the degree of motion sickness for the group with at least 8 h of scopolamine application prior to sea travel. Therefore, the transdermal scopolamine system should be applied at least 8 h before potentially disturbing motion to provide adequate prophylaxis against motion sickness. We found no significant difference in motion sickness susceptibility between men and women, in contrast to earlier reports.

  12. Procyanidins extracted from the lotus seedpod ameliorate scopolamine-induced memory impairment in mice.

    PubMed

    Xu, Jiqu; Rong, Shuang; Xie, Bijun; Sun, Zhida; Zhang, Li; Wu, Hailei; Yao, Ping; Zhang, Yunjian; Liu, Liegang

    2009-12-01

    The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) in mice. The capacities of memory and learning were evaluated by the Morris water maze and the step-down avoidance test. LSPC (50, 100, 150 mg/kg BW, p.o.) significantly reversed scopolamine-induced learning and memory impairments in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. In the step-down avoidance test, LSPC (50, 100, 150 mg/kg BW, p.o.) treatment significantly reduced the number of errors and shortened latency compared with that of scopolamine. In addition, LSPC was also found to inhibit acetyl cholinesterase (AChE) activity. These results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by AD and aging.

  13. 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. PMID

  14. 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

  15. 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.

  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. 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

  18. 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

  19. Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

    PubMed

    Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

    2016-08-30

    The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. PMID:27366831

  20. 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

  1. 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

  2. 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…

  3. Chlorpyrifos-induced hypothermia and vasodilation in the tail of the rat: blockade by scopolamine.

    PubMed

    Gordon, C J; Yang, Y L

    2000-07-01

    Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos-induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos-induced hypothermia. Tc and motor activity were monitored by telemetry in female Long-Evans rats maintained at an ambient temperature (Ta) of 25 degrees. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t)) concomitant with a 0.5 degrees reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS. PMID:10987209

  4. 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.

  5. 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. PMID:27483466

  6. 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

  7. 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

  8. 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

  9. Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice.

    PubMed

    Lim, Dong Wook; Son, Hyun Jung; Um, Min Young; Kim, In-Ho; Han, Daeseok; Cho, Suengmok; Lee, Chang-Ho

    2016-08-05

    In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice.

  10. Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice.

    PubMed

    Lim, Dong Wook; Son, Hyun Jung; Um, Min Young; Kim, In-Ho; Han, Daeseok; Cho, Suengmok; Lee, Chang-Ho

    2016-01-01

    In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice. PMID:27527139

  11. Involvement of dorsal hippocampal alpha-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task.

    PubMed

    Azami, Nasrin-Sadat; Piri, Morteza; Oryan, Shahrbano; Jahanshahi, Mehrdad; Babapour, Vahab; Zarrindast, Mohammad-Reza

    2010-05-01

    The present study evaluated the possible role of alpha-adrenergic receptors of the dorsal hippocampus on scopolamine-induced amnesia and scopolamine state-dependent memory in adult male Wistar rats. The 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 to measure step-through latency. Results indicate that post-training or pre-test intra-CA1 administration of scopolamine (1 and 2 microg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 microg/rat) was reversed by pre-test administration of the scopolamine that is due to a state-dependent effect. Interestingly, pre-test intra-CA1 microinjection of alpha1-adrenergic agonist, phenylephrine (1 and 2 microg/rat) or alpha2-adrenergic agonist, clonidine improved post-training scopolamine (2 microg/rat)-induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25, 0.5 and 1 microg/rat) or clonidine (0.25, 0.5 and 1 microg/rat) with an ineffective dose of scopolamine (0.25 microg/rat), synergistically improved memory performance impaired by post-training scopolamine. On the other hand, pre-test injection of alpha1-receptors antagonist prazosin (1 and 2 microg/rat) or alpha2-receptors antagonist yohimbine (1 and 2 microg/rat) prevented the restoration of memory by pre-test scopolamine. It is important to note that pre-test intra-CA1 administration of the same doses of prazosin or yohimbine, alone did not affect memory retrieval. These results suggest that alpha1- and alpha2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory.

  12. 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.

  13. 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.

  14. Influence of Antipsychotic and Anticholinergic Loads on Cognitive Functions in Patients with Schizophrenia

    PubMed Central

    Rehse, Michael; Bartolovic, Marina; Baum, Katlehn; Richter, Dagmar; Weisbrod, Matthias; Roesch-Ely, Daniela

    2016-01-01

    Many patients with schizophrenia show cognitive impairment. There is evidence that, beyond a certain dose of antipsychotic medication, the antipsychotic daily dose (ADD) may impair cognitive performance. Parallel to their D2 receptor antagonism, many antipsychotics show a significant binding affinity to cholinergic muscarinic receptors. Pharmacological treatment with a high anticholinergic daily dose (CDD) significantly impairs attention and memory performance. To examine the relationships between individual cognitive performance and ADD and/or CDD, we conducted a retrospective record-based analysis of a sample of n = 104 in patients with a diagnosis of schizophrenia, all of whom had completed a comprehensive neuropsychological test battery. To calculate the individual ADD and CDD, the medication at the time of testing was converted according to equivalence models. After extracting five principal cognitive components, we examined the impact of ADD and CDD on cognitive performance in the medicated sample and subgroups using multiple regression analysis. Finally, locally weighted scatterplot smoothing (Loess) was applied to further explore the course of cognitive performance under increasing dosage. Results showed significant negative effects of ADD on performance in tests of information processing speed and verbal memory. No effects were found for CDD. The potential neuropsychopharmacological and clinical implications are discussed. PMID:27144021

  15. 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.

  16. A Review of the Role of Anticholinergic Activity in Lewy Body Disease and Delirium.

    PubMed

    Kitajima, Yuka; Hori, Koji; Konishi, Kimiko; Tani, Masayuki; Tomioka, Hiroi; Akashi, Norihisa; Hosoi, Misa; Inamoto, Atsuko; Hasegawa, Sayaka; Kikuchi, Nodoka; Takahashi, Akari; Hachisu, Mitsugu

    2015-01-01

    We have previously proposed a hypothesis in which we argue that anticholinergic activity (AA) appears endogenously in Alzheimer's disease (AD). Acetylcholine (ACh) controls both cognitive function and inflammation. Consequently, when the downregulation of ACh reaches critical levels, the inflammatory system is upregulated and proinflammatory cytokines with AA appear. However, factors other than downregulation of ACh can produce AA; even if ACh downregulation does not reach critical levels, AA can still appear if one of these other AA-producing factors is added. These factors can include neurocognitive disorders other than AD, such as delirium and Lewy body disease (LBD). In delirium, ACh downregulation fails to reach critical levels, but AA appears due to the use of medicines, physical illnesses or mental stress (termed 'AA inserts'). In LBD, we speculate that AA appears endogenously, even in the absence of severe cognitive dysfunction, for 2 reasons. One reason is that patterns of ACh deterioration are different in LBD from those in AD, with synergistic actions between amyloid and α-synuclein thought to cause additional or severe symptoms that accelerate the disease course. The second reason is that AA occurs through disinhibition by reduced cortisol levels that result from severe autonomic parasympathetic dysfunction in LBD.

  17. 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

  18. Histaminergic response to Coriolis stimulation: implication for transdermal scopolamine therapy of motion sickness.

    PubMed

    Wang, E T; Zhou, D R; He, L H

    1992-07-01

    The blood levels of histamine and 5-hydroxytryptamine (5-HT) in 10 subjects, with or without administration of the transdermal therapeutic system of scopolamine (TTS-S), were measured following motion sickness (MS) induced by Coriolis stimulation. Histamine and 5-HT were assayed using the fluorometric method. The results demonstrated that the blood levels of histamine increased significantly following MS and were even higher in the subjects using TTS-S, but we found neither significant changes in the blood levels of 5-HT following MS nor any effect of TTS-S on it. The results suggest that histamine contributes to the development of MS, and scopolamine may exert its anti-MS action by affecting the histaminergic system as well as the acetylcholinergic system; there may not be a definite relation between 5-HT and the development of MS.

  19. The Effects of Loranthus parasiticus on Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Weon, Jin Bae; Lee, Jiwoo; Eom, Min Rye; Jung, Youn Sik; Ma, Choong Je

    2014-01-01

    This study is undertaken to evaluate cognitive enhancing effect and neuroprotective effect of Loranthus parasiticus. Cognitive enhancing effect of Loranthus parasiticus was investigated on scopolamine-induced amnesia model in Morris water maze test and passive avoidance test. We also examined the neuroprotective effect on glutamate-induced cell death in HT22 cells by MTT assay. These results of Morris water maze test and passive avoidance test indicated that 10 and 50 mg/kg of Loranthus parasiticus reversed scopolamine-induced memory deficits. Loranthus parasiticus also protected against glutamate-induced cytotoxicity in HT22 cells. As a result of in vitro test for elucidating possible mechanism, Loranthus parasiticus inhibited AChE activity, ROS production, and Ca2+ accumulation. Loranthus parasiticus showed memory enhancing effect and neuroprotective effect and these effects may be related to inhibition of AChE activity, ROS level, and Ca2+ influx. PMID:25045391

  20. 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.

  1. 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.

  2. 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. PMID:27149969

  3. Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice

    PubMed Central

    Zhou, Heng; Xue, Wei; Chu, Shi-feng; Wang, Zhen-zhen; Li, Chuang-jun; Jiang, Yi-na; Luo, Lin-ming; Luo, Piao; Li, Gang; Zhang, Dong-ming; Chen, Nai-hong

    2016-01-01

    Aim: Recent studies show that the extract of a Chinese herb Polygalae Radix exerts cognition-enhancing actions in rats and humans. The aim of this study was to characterize the pharmacological profiles of active compounds extracted from Polygalae Radix. Methods: Two fractions P3 and P6 and two compounds PTM-15 and polygalasaponin XXXII (PGS32) were prepared. Neuroprotective effects were evaluated in primary cortical neurons exposed to high concentration glutamate, serum deficiency or H2O2. Anti-dementia actions were assessed in scopolamine-induced amnesia in mice using step-through avoidance tests and channel water maze tests. After conducting the channel water maze tests, TrkB phosphorylation in mouse hippocampus was detected using Western blotting. Long-term potentiation (LTP) was induced in the dentate gyrus in adult rats; PGS32 (5 μL 400 μmol/L) was injected into the lateral cerebral ventricle 20 min after high frequency stimulation (HFS). Results: Compared to the fraction P6, the fraction P3 showed more prominent neuroprotective effects in vitro and cognition-enhancing effects in scopolamine-induced amnesia in mice. One active compound PGS32 in the fraction P3 exerted potent cognition-enhancing action: oral administration of PGS32 (0.125 mg·kg−1·d−1) for 19 days abolished scopolamine-induced memory impairment in mice. Furthermore, PGS32 (0.5 and 2 mg·kg−1·d−1) significantly stimulated the phosphorylation of TrkB in the hippocampus. Intracerebroventricular injection of PGS32 significantly enhanced HFS-induced LTP in the dentate gyrus of rats. Conclusion: PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia. PMID:27180981

  4. Evaluation of the effect of Cyperus rotundus L. in scopolamine-induced learning deficit in mice

    PubMed Central

    Rabbani, Mohammed; Ghannadi, Alireza; Malekian, Nahid

    2014-01-01

    Background: Cyperus rotundus L. was used in traditional Iranian medicine to treat memory and cognition disorders. The present study was aimed at investigating the effect of the extract and essential oil of C. rotundus on memory dysfunction. Materials and Methods: Cognition was evaluated using the object recognition task that was composed of a square wooden open field box with different shape objects. The test was consisted of three sections: 15 min exploration, first trial for 12 min and second one for 5 min. In the second trial the difference in exploration between a previously seen object and novel one, was considered as an index of memory performance (recognition index). Memory deficit was induced by scopolamine (0.5 mg/kg) before injection of plant extracts and essential oil. Results: Rivastigmine at 0.6 mg/kg reversed the scopolamine induced memory dysfunction in mice (P < 0.05). On the contrary, neither the hydroalcholic extracts (100, 200, 400 mg/kg) nor the polyphenolic extract (50, 100, 200 mg/kg) and essential oil (10, 20, 40 mg/kg) of C. rotundus produced significant improvement of memory dysfunction. The fact that rivastigmine reversed the scopolamine-induced memory dysfunction confirms the validity of this memory paradigm. Conclusion: Using the current method of the memory evaluation, none of the tested doses of the plant extract or essential oil changed the memory status of the animals, indicating either a lack of effective ingredient or unsuitable method for evaluation. PMID:25371874

  5. The memory-enhancing effect of erucic acid on scopolamine-induced cognitive impairment in mice.

    PubMed

    Kim, Eunji; Ko, Hae Ju; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Ha Neul; Woo, Eun-Rhan; Ryu, Jong Hoon

    2016-03-01

    Erucic acid is a monounsaturated omega-9 fatty acid isolated from the seed of Raphanus sativus L. that is known to normalize the accumulation of very long chain fatty acids in the brains of patients suffering from X-linked adrenoleukodystrophy. Here, we investigated whether erucic acid enhanced cognitive function or ameliorated scopolamine-induced memory impairment using the passive avoidance, Y-maze and Morris water maze tasks. Erucic acid (3mg/kg, p.o.) enhanced memory performance in normal naïve mice. In addition, erucic acid (3mg/kg, p.o.) ameliorated scopolamine-induced memory impairment, as assessed via the behavioral tasks. We then investigated the underlying mechanism of the memory-enhancing effect of erucic acid. The administration of erucic acid increased the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K), protein kinase C zeta (PKCζ), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and additional protein kinase B (Akt) in the hippocampus. These results suggest that erucic acid has an ameliorative effect in mice with scopolamine-induced memory deficits and that the effect of erucic acid is partially due to the activation of PI3K-PKCζ-ERK-CREB signaling as well as an increase in phosphorylated Akt in the hippocampus. Therefore, erucic acid may be a novel therapeutic agent for diseases associated with cognitive deficits, such as Alzheimer's disease. PMID:26780350

  6. Vinpocetine Improves Scopolamine Induced Learning and Memory Dysfunction in C57 BL/6J Mice.

    PubMed

    Shang, Yu; Wang, Lei; Li, Yue; Gu, Pei-Fei

    2016-09-01

    Vinpocetine is an inhibitor of phosphodiesterase type 1 (PDE1), which has been used for treating stroke for over 40 years. However, according to current clinical dosage and treatment period, its direct effect on memory is unclear. In this study, we investigated whether vinpocetine could reverse the scopolamine (SCO)-induced cognitive deficits in animals. Behavioral experiments, including open field, Y-maze, and fear conditioning tests were used to determine the possible role of vinpocetine on scopolamine-induced memory dysfunction. In the open field and Y-maze tests, there were significant differences between the control (CON) group and SCO group. Vinpocetine (4 mg/kg) administration for consecutive 28 d significantly improved the scopolamine-induced memory dysfunction. In the fear conditioning test, vinpocetine (2, 4 mg/kg) administration had certain beneficial effect on emotional memory. Our results suggest that vinpocetine could improve cognitive function in memory deficient mice and high clinic dosage might be better.

  7. Cognitive-Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice.

    PubMed

    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.

  8. 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

  9. 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

    2012-04-01

    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

  10. 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

    2012-04-01

    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

  11. Assessment of Cognitive Dysfunction Caused by Anticholinergic Burden in Japanese Alzheimer's Disease Patients, Using the Most Commonly Used Scales in Japan.

    PubMed

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

    2015-11-01

    Anticholinergic activity (AA) is generally thought to cause cognitive dysfunction, especially in Alzheimer's disease (AD), one of the neurocognitive disorders related to memory disturbances. Therefore, it is important to evaluate cognitive functions to determine whether they are associated with anticholinergic burden. In Japan, the most frequently used cognitive scale for evaluating cognitive functions is the revised version of Hasegawa's Dementia Rating Scale (HDS-R). However, the relationship between anticholinergic burden and cognitive functions has not been previously examined using the HDS-R. Therefore, here we used the HDS-R to evaluate the relationship between serum anticholinergic activity (SAA) and cognitive functions in 76 patients with AD, 26 of whom had positive SAA [SAA (+)] with a mean of 4.14 ± 2.70 nM. Total scores for orientations to time and place, registration, and recall were significantly lower in the SAA (+) group than in the SAA (-) group (P < 0.05), suggesting potential relationships between SAA and disorientations to time and place in current surroundings as well as memory disturbances. Thus, the disorientations to time and place might explain the clinical features of confusion in current surroundings caused by anticholinergic burden in AD. PMID:26785521

  12. An atypical pattern of accumulation of scopolamine and other tropane alkaloids and expression of alkaloid pathway genes in Hyoscyamus senecionis.

    PubMed

    Dehghan, Esmail; Shahriari Ahmadi, Farajollah; Ghotbi Ravandi, Elnaz; Reed, Darwin W; Covello, Patrick S; Bahrami, Ahmad Reza

    2013-09-01

    A cDNA encoding hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), a bifunctional enzyme catalyzing the last two steps in the scopolamine biosynthetic pathway, was isolated from Hyoscyamus senecionis, a medicinal plant endemic to the Iranian plateau. Expression analysis indicates that Hsh6h is expressed in all tested organs of H. senecionis including roots, rhizomes, leaves, stems and flowers unlike the other tropane alkaloid producing species. In parallel to this, in leaves, levels of scopolamine, the product of H6H, were higher than the substrate hyoscyamine. These data suggest that not only does the conversion of hyoscyamine to scopolamine take place in the root, followed by translocation to aerial parts, but also accumulated hyoscyamine in the aerial parts may be converted to scopolamine by activity of HsH6H. Analysis of expression profiles of putrescine N-methyltransferase and tropinone reductase I and II genes also indicates the organ-independent expression of these genes. Here we also introduce H. senecionis as an important tropane alkaloid producing species with its thick underground parts as a source of hyoscyamine, while its leaves can be considered as a source of scopolamine.

  13. [Determination of hyoscyamine and scopolamine in serum and urine of humans by liquid chromatography with tandem mass spectrometry].

    PubMed

    Konishi, Tomohiko; Akaki, Kouichi; Hatano, Kazuhiro

    2008-08-01

    A simple method was developed for the analysis of hyoscyamine and scopolamine in human serum and urine using liquid chromatography with tandem mass spectrometry (LC/MS/MS). Hyoscyamine and scopolamine in serum and urine were cleaned up with an Oasis HLB cartridge and a PSA cartridge. The LC separation was carried out on an ODS column, using linear gradient elution with 5 mmol/L IPCC-MS3-methanol as the mobile phase. The mass spectral acquisition was done in the positive ion mode by applying selected reaction monitoring (SRM). The recoveries of hyoscyamine and scopolamine were 86.0-105% from human serum and urine fortified at 0.2 ng/mL and 10 ng/mL. The detection limits of hyoscyamine and scopolamine were 0.02 ng/mL. Four serum and three urine samples of humans poisoned by eating Datura innoxia Mill. were analyzed by this method. Hyoscyamine and scopolamine were detected at the levels of 0.45-3.5 ng/mL in all serum samples and 170-670 ng/mL in all urine samples.

  14. In vivo investigation of the neuroprotective property of Convolvulus pluricaulis in scopolamine-induced cognitive impairments in Wistar rats

    PubMed Central

    Bihaqi, Syed Waseem; Singh, Avninder Pal; Tiwari, Manisha

    2011-01-01

    Aim: To investigate the neuroprotective effect of Convolvulus pluricaulis aqueous extract (AE) against scopolamine (1 mg/kg body weight (bwt))-induced neurotoxicity in the cerebral cortex of male Wistar rats. Materials and Methods: The study was carried out on male Wistar rats (age matched, weight 250 ± 20 g). The present study investigated cognitive-enhancing property of AE using Elevated plus maze (EPM) (transfer latency [TL]) and Morris water maze (MWM). Besides evaluating the effect of extract on neurochemical enzymes, in vivo antioxidant and free radical scavenging activities were also screened. All the measured parameters were compared with rivastigmine tartrate (1 mg/kg bwt) which was taken as standard. Results: Pretreatment of rats with AE (150 mg/kg bwt) significantly reduced scopolamine-induced increase in the TL in EPM, whereas in MWM, administration of extract improved the impairment of spatial memory induced by scopolamine. The activity of acetylcholinesterase (AChE) was significantly inhibited by extract within the cortex and hippocampus. Reduced activities or contents of glutathione reductase, superoxide dismutase, and reduced glutathione within the cortex and hippocampus induced by scopolamine were elevated by the extract. Taken together, it could be postulated that extract may exert its potent-enhancing activity through both anti-AChE and antioxidant action. Conclusion: AE possesses neuroprotective potential, thus validating its use in alleviating toxic effects of scopolamine. PMID:22021993

  15. Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms.

    PubMed

    Fan, Ying; Hu, Jinfeng; Li, Jing; Yang, Zhao; Xin, Xianliang; Wang, Jia; Ding, Jian; Geng, Meiyu

    2005-02-21

    In this study we evaluated the effect of a novel, marine-derived, acidic oligosaccharide on scopolamine-induced amnesia in rats using the Morris water maze test. The results show that 30-day administration of this oligosaccharide, referred to as acidic oligosaccharide sugar chain (AOSC), to rats attenuates memory impairment by scopolamine, as evaluated by shortened escape latency, swimming distance, and increased swimming time of rats with memory impairment induced by scopolamine in the quadrant where the platform is placed. The data additionally suggest that an appropriate dose of scopolamine, a traditional muscarinic receptor antagonist, elevates oxidative damage in brain, characterized by inactivation of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and consequently, inhibition of ATPase in the hippocampus and cerebral cortex. AOSC ameliorates oxidative injuries caused by scopolamine by increasing the activities of SOD, GSH-Px, and ATPase. Further investigation by flow cytometry revealed that AOSC significantly reduces the overloading of intracellular free calcium ion ([Ca2+]i), thus suppressing apoptosis induced by H2O2 in human neuroblastoma SH-SY5Y cells. These findings suggest that AOSC can induce cognitive improvement via its antioxidant activity.

  16. Dissociation between memory reactivation and its behavioral expression: scopolamine interferes with memory expression without disrupting long-term storage.

    PubMed

    Caffaro, Pedro Alejandro; Suárez, Luis Daniel; Blake, Mariano Gillermo; Delorenzi, Alejandro

    2012-10-01

    The reconsolidation hypothesis has challenged the traditional view of fixed memories after consolidation. Reconsolidation studies have disclosed that the mechanisms mediating memory retrieval and the mechanisms that underlie the behavioral expression of memory can be dissociated, offering a new prospect for understanding the nature of experimental amnesia. The muscarinic antagonist scopolamine has been used for decades to induce experimental amnesias The goal of the present study is to determine whether the amnesic effects of scopolamine are due to storage (or retrieval) deficits or, alternatively, to a decrease in the long-term memory expression of a consolidated long-term memory. In the crab Chasmagnathus memory model, we found that scopolamine-induced amnesia can be reverted by facilitation after reminder presentation. This recovery of memory expression was reconsolidation specific since a reminder that does not triggers reconsolidation process did not allow the recovery. A higher dose (5 μg/g) of scopolamine induced an amnesic effect that could not be reverted through reconsolidation, and thus it can be explained as an interference with memory storage and/or retrieval mechanisms. These results, showing that an effective amnesic dose of scopolamine (100 ng/g) negatively modulates long-term memory expression but not memory storage in the crab Chasmagnathus, are consistent with the concept that dissociable processes underlie the mechanisms mediating memory reactivation and the behavioral expression of memory.

  17. Comparative Effect of Lisinopril and Fosinopril in Mitigating Learning and Memory Deficit in Scopolamine-Induced Amnesic Rats.

    PubMed

    Deb, Debasree; Bairy, K L; Nayak, Veena; Rao, Mohandas

    2015-01-01

    Lisinopril and fosinopril were compared on scopolamine-induced learning and memory deficits in rats. A total of eighty-four male Wistar rats were divided into seven groups. Group I received 2% gum acacia orally for 4 weeks, group II received normal saline, and group III received scopolamine (2 mg/kg/ip) as single dose. Groups IV and V received lisinopril ( 0.225 mg/kg and 0.45 mg/kg), while Groups VI and VII received fosinopril (0.90 mg/kg and 1.80 mg/kg), respectively, orally for four weeks, followed by scopolamine (2 mg/kg/ip) given 45 minutes prior to experimental procedure. Evaluation of learning and memory was assessed by using passive avoidance, Morris water maze, and elevated plus maze tests followed by analysis of hippocampal morphology and quantification of the number of surviving neurons. Scopolamine induced marked impairment of memory in behavioral tests which correlated with morphological changes in hippocampus. Pretreatment with fosinopril 1.80 mg/kg was found to significantly ameliorate the memory deficits and hippocampal degeneration induced by scopolamine. Fosinopril exhibits antiamnesic activity, indicating its possible role in preventing memory deficits seen in dementia though the precise mechanism underlying this effect needs to be further evaluated. PMID:26300914

  18. Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. (Reannouncement with new availability information)

    SciTech Connect

    von Bredow, J.; Corcoran, K.; Maitland, G.; Kaminskis, A.; Adams, N.

    1991-12-31

    Pretreatment of nonhuman primates with physostigmine (Phy) and scopolamine or physostigmine and trihexyphenidyl 25 min before exposure to 2 LD50 soman im resulted in complete survival without convulsions or loss of consciousness. When identically pretreated animals were challenged with 5 LD50s of soman followed by atropine and 2-PAM therapy 1 min later, all animals experienced a loss of consciousness for approximately 10 min followed by functional recovery within an additional 20 min. These findings indicated that a pretreatment regimen composed of Phy and cholinolytic is capable of protecting primates from an absolute lethal dose of soman with rapid recovery from incapacitation. Physostigmine, nerve agent pretreatment, cynomolgus monkeys soman (GD).

  19. The potency and efficacy of anticholinergics to inhibit haloperidol-induced catalepsy in rats correlates with their rank order of affinities for the muscarinic receptor subtypes.

    PubMed

    Erosa-Rivero, Helena B; Bata-García, José L; Alvarez-Cervera, Fernando J; Heredia-López, Francisco J; Góngora-Alfaro, José L

    2014-06-01

    Extrapyramidal syndromes (EPS) caused by antipsychotic therapy are currently treated with anticholinergics that lack selectivity for the five muscarinic receptor subtypes. Since these receptors are heterogeneously expressed among the different classes of striatal neurons and their afferents, it can be expected that their simultaneous blockade will cause distinct, sometimes opposed, effects within the striatal circuitry. In order to test the hypothesis that the differential blockade of the muscarinic receptor subtypes would influence their potency and efficacy to prevent EPS, here we tested four anticholinergics with varying order of affinities for the muscarinic receptor subtypes, and compared their dose-response curves to inhibit haloperidol-induced catalepsy in male rats. Drugs were applied into the lateral ventricle 15 min before haloperidol (2 mg/kg, s.c.). Catalepsy was measured in the bar test at 15 min intervals during 5 h. The preferential M1/M4 antagonist pirenzepine (3, 10, 30, 100, and 300 nmol) caused a dose-dependent inhibition of catalepsy intensity: ED50 = 5.6 nmol [95% CI, 3.9-8.1], and latency: ED50 = 5.6 nmol [95% CI, 3.7-8.6]. Pirenzepine had the steepest dose-response curve, producing maximal inhibition (84 ± 5%) at the dose of 10 nmol, while its effect tended to reverse at higher doses (62 ± 11%). The purported M1/M3 antagonist 4-DAMP (30, 100, and 300 nmol) also caused a dose-dependent inhibition of catalepsy intensity: ED50 = 29.5 nmol [95% CI, 7.0 to 123.0], and latency: ED50 = 28.5 nmol [95% CI, 2.2 to 362.0]. However, the curve for 4-DAMP had a less pronounced slope, reaching its maximal effect (63 ± 14%) at the dose of 300 nmol. The M2/M4 antagonist AF-DX 116 (10, 30, and 300 nmol) only caused a partial inhibition of catalepsy (30 ± 11%) at the dose of 30 nmol, but this changed to a non-significant increment (15 ± 10%) at the dose of 100 nmol. The alleged M4 antagonist tropicamide (30, 100, 300, and

  20. 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.

  1. 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. PMID:27135818

  2. 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. PMID:26033423

  3. Mirabegron in overactive bladder patients: efficacy review and update on drug safety

    PubMed Central

    Warren, Katherine; Burden, Helena; Abrams, Paul

    2016-01-01

    Overactive bladder is a common condition, which significantly affects people’s quality of life. The use of anticholinergic medication has been the mainstay of managing overactive bladder when conservative measures are not enough. Many patients stop anticholinergic medication because of the side effects and more recently the concerns about the effect of an anticholinergic burden and the development of dementia have been studied. Activation of β3 adrenoceptors has been shown to relax the detrusor muscle and subsequently lead to the development of the first β3 adrenoceptor agonist. Mirabegron is the first drug in this class to be approved for the use in overactive bladder. It has been extensively studied in phase II and III trials and has significant improvement in key overactive bladder parameters when compared with placebo. The incidence of side effects such as constipation, hypertension and tachycardia were comparable to anticholinergic medication but there was significantly less dry mouth incidence in the mirabegron groups. Mirabegron has been shown to be used safely in combination with solifenacin and tamsulosin. Head-to-head studies comparing efficacy and safety of mirabegron with anticholinergic medication would further help in the management strategy for overactive bladder. PMID:27695622

  4. Mirabegron in overactive bladder patients: efficacy review and update on drug safety

    PubMed Central

    Warren, Katherine; Burden, Helena; Abrams, Paul

    2016-01-01

    Overactive bladder is a common condition, which significantly affects people’s quality of life. The use of anticholinergic medication has been the mainstay of managing overactive bladder when conservative measures are not enough. Many patients stop anticholinergic medication because of the side effects and more recently the concerns about the effect of an anticholinergic burden and the development of dementia have been studied. Activation of β3 adrenoceptors has been shown to relax the detrusor muscle and subsequently lead to the development of the first β3 adrenoceptor agonist. Mirabegron is the first drug in this class to be approved for the use in overactive bladder. It has been extensively studied in phase II and III trials and has significant improvement in key overactive bladder parameters when compared with placebo. The incidence of side effects such as constipation, hypertension and tachycardia were comparable to anticholinergic medication but there was significantly less dry mouth incidence in the mirabegron groups. Mirabegron has been shown to be used safely in combination with solifenacin and tamsulosin. Head-to-head studies comparing efficacy and safety of mirabegron with anticholinergic medication would further help in the management strategy for overactive bladder.

  5. Effects of atropine, scopolamine and xylazine on the placement of an orally administered magnet in cows.

    PubMed

    Braun, U; Gansohr, B; Flückiger, M

    2003-03-01

    This study was carried out to determine whether the administration of atropine, scopolamine or xylazine to cows before the administration of a magnet orally would help to position it in the reticulum. The transit time of the magnet through the oesophagus was also measured. Sixty Swiss Braunvieh cows were examined by radiography and ultrasonography to locate the reticulum. They were then divided into six groups of 10. Before the administration of the magnet, a control group received 4 ml saline solution subcutaneously, one group received 0.10 mg/kg of atropine subcutaneously, a second received 0.05 mg/kg of atropine intravenously, a third received 0.15 mg/kg of scopolamine intravenously, a fourth group received 0.02 mg/kg of xylazine intravenously, and the cows in the fifth group were positioned so that their forelimbs were 30 cm lower than their hindlimbs during the administration of the magnet. The passage of the magnet through the oesophagus was timed with a stopwatch and monitored with a compass. In the control group the magnet passed through in less than 60 seconds, but in four of the cows receiving either atropine or xylazine intravenously, or having their forelimbs positioned lower than their hindlimbs, it took longer than 60 seconds. In the cows receiving atropine subcutaneously or scopolamine intravenously, it took the same time as in the control group. All the cows were radiographed one-and-a-half hours after the administration of the magnet to determine its location. In seven of the 10 cows in the control group, the magnet was located in the reticulum, but in the other three it was in the cranial dorsal blind sac of the rumen. In the other five groups the magnet was located in the reticulum of between four and seven of the 10 cows, but in the cranial dorsal sac of the rumen, the rumen or in other sites in the other cows.

  6. Serial position effect and selective amnesia induced by scopolamine in mice.

    PubMed

    Watanabe, S; Yanagisawa, N

    2000-02-01

    Mice were trained to run through a maze with six gates, each consisting of three doors--two locked and one unlocked. They learned to choose a correct (unlocked) door at the gates close to the beginning and end better than in the middle, showing the primacy and recency effects of serial learning. A low dose of scopolamine unexpectedly enhanced the primacy effect, while a high dose impaired learning in general. The enhancement of the primacy effect can be explained in terms of reduction of retroactive interference.

  7. Testing for atropine and scopolamine in hair by LC-MS-MS after Datura inoxia abuse.

    PubMed

    Kintz, Pascal; Villain, Marion; Barguil, Yann; Charlot, Jean-Yves; Cirimele, Vincent

    2006-09-01

    Datura inoxia belongs to the family of Solanaceae. This is a very common plant in New Caledonia that contains two main toxic alkaloids, l-atropine and l-scopolamine. In this study, we report the case of a 20-year-old male admitted to an Emergency Unit after consumption of 6 dried flowers in hot water for hallucinations, mydriasis, and agitation associated with tachycardia and increase of systolic blood pressure to 180. Full recovery was observed after one week. Three weeks later, a lock of about 80 hairs (200 mg) was collected from the subject in vertex posterior with scissors to be tested for both atropine and scopolamine. After decontamination with dichloromethane, a strand of hair was segmented into three parts, cut into small segments (< 1 mm), incubated overnight in 1 mL pH 8.4 phosphate buffer in the presence of 2.5 ng atropine-d(3), the internal standard, then extracted with 5 mL dichloromethane/isopropanol/n-heptane (50:17:33). The residue was reconstituted in 100 microL of methanol, from which 10 microL was injected into an XTerra MS C18 column (100 x 2.1 mm, 3.5 microm) eluted with a gradient of acetonitrile and formate buffer delivered at a flow rate of 0.2 mL/min. A Quattro Micro triple-quadrupole mass spectrometer (MS) was used for analyses. Ionization was achieved using electrospray in the positive ionization mode. For each compound, detection was related to two daughter ions (atropine: m/z 290.2 to 124.0 and 92.9; atropine-d(3): m/z 293.1 to 127.0 and 92.9; scopolamine: m/z 304.1 to 138.0 and 156.0). Although atropine was never detected (limit of detection = 2 pg/mg), scopolamine was identified in the three segments, in the range 14 to 48 pg/mg. The absence of atropine in hair is consistent with its very low dosage in the flower of Datura inoxia. Hair segmentation indicated that the subject was previously exposed on several occasions to the plant. Liquid chromatography-tandem MS appears to be a necessity for testing tropane alkaloids of the Datura

  8. Drug Burden Index in older adults: theoretical and practical issues

    PubMed Central

    Kouladjian, Lisa; Gnjidic, Danijela; Chen, Timothy F; Mangoni, Arduino A; Hilmer, Sarah N

    2014-01-01

    Anticholinergic and sedative medications are commonly used in older adults and are associated with adverse clinical outcomes. The Drug Burden Index was developed to measure the cumulative exposure to these medications in older adults and its impact on physical and cognitive function. This narrative review discusses the research and clinical applications of the Drug Burden Index, and its advantages and limitations, compared with other pharmacologically developed measures of high-risk prescribing. PMID:25246778

  9. Role of percutaneous posterior tibial nerve stimulation either alone or combined with an anticholinergic agent in treating patients with overactive bladder

    PubMed Central

    Kızılyel, Sadık; Karakeçi, Ahmet; Ozan, Tunç; Ünüş, İhsan; Barut, Osman; Onur, Rahmi

    2015-01-01

    Objective To evaluate the efficacy of percutaneous tibial nerve stimulation (PTNS), either alone or combined with an anticholinergic agent, in treating patients with an overactive bladder (OAB) in whom previous conservative treatment failed. Material and methods In this study, we included a total of 30 female patients with OAB in whom all conventional therapies failed between January 2010 and April 2011. Patients were randomly divided into three groups: Group 1, PTNS group; Group 2, patients receiving an anticholinergic agent; and Group 3, patients receiving both PTNS and anticholinergic agent. PTNS treatment continued for 12 weeks with each session lasting 30 min. Results All parameters of the bladder diary significantly improved in all groups (p<0.05). Similarly, all scores measured by questionnaires (UDI-6, IIQ-7, and OABSS) revealed significant improvements in all groups. When the improvements in symptoms were compared among the groups, there was a statistically significantly higher improvement in groups 1 and 3 than in Group 2. Conclusion PTNS is a safe, simple, and minimally invasive treatment modality in patients with OAB, and it may be suggested either alone or in combination with anticholinergics when conventional treatments fail. PMID:26623150

  10. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  11. The effects of Anethum graveolens essence on scopolamine-induced memory impairment in mice.

    PubMed

    Mesripour, Azadeh; Rafieian-Kopaei, Mahmoud; Bahrami, Bahareh

    2016-01-01

    Since Anethum graveolens (Dill) has phytoestrogenic compounds and it is proven that estrogens exert beneficial effects on cognition; the aim of this study was to understand if this plant can improve memory performance. Male Balb/c mice weighing 25-30 g were used in this study and memory was assessed by the novel object recognition task. In this method, the difference in the exploration time between a familiar object and a novel object is taken as an index of memory performance (recognition index, RI). Scopolamine significantly reduced memory index (RI = -15.5% ± 3.0). Dill essence (100 mg/kg, ip) prevented the harmful effects of scopolamine on memory (RI = 40% ± 5.5), thus RI did not differ with control animals (RI = 50% ± 5.8). In addition, 17-β estradiol also prevented memory impairment in animals (0.2 mg/kg, ip; RI = 35.8% ± 6.5). Nevertheless, the beneficial effects of dill essence were antagonized by prior injection of tamoxifen (1 mg/kg, ip; RI = -30% ± 7.8). Although phytoesrogens are not steroids, the beneficial effect of dill on memory, at least in part, may have been achieved by estrogenic receptors present in the brain. Thus dill essence could be promising in improving memory and cognition, mainly in postmenopausal women. PMID:27168754

  12. The effects of Anethum graveolens essence on scopolamine-induced memory impairment in mice

    PubMed Central

    Mesripour, Azadeh; Rafieian-Kopaei, Mahmoud; Bahrami, Bahareh

    2016-01-01

    Since Anethum graveolens (Dill) has phytoestrogenic compounds and it is proven that estrogens exert beneficial effects on cognition; the aim of this study was to understand if this plant can improve memory performance. Male Balb/c mice weighing 25-30 g were used in this study and memory was assessed by the novel object recognition task. In this method, the difference in the exploration time between a familiar object and a novel object is taken as an index of memory performance (recognition index, RI). Scopolamine significantly reduced memory index (RI = -15.5% ± 3.0). Dill essence (100 mg/kg, ip) prevented the harmful effects of scopolamine on memory (RI = 40% ± 5.5), thus RI did not differ with control animals (RI = 50% ± 5.8). In addition, 17-β estradiol also prevented memory impairment in animals (0.2 mg/kg, ip; RI = 35.8% ± 6.5). Nevertheless, the beneficial effects of dill essence were antagonized by prior injection of tamoxifen (1 mg/kg, ip; RI = -30% ± 7.8). Although phytoesrogens are not steroids, the beneficial effect of dill on memory, at least in part, may have been achieved by estrogenic receptors present in the brain. Thus dill essence could be promising in improving memory and cognition, mainly in postmenopausal women. PMID:27168754

  13. Antimotion-sickness efficacy of scopolamine 12 and 72 hours after transdermal administration

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

    The antimotion sickness remedy, transdermal therapeutic system-scopolamine, administered in this experiment was scheduled to deliver 1.0 mg of scopolamine over a period of 3 d, and this paper compares its efficacy 12 and 72 h after administration. In a double-blind study, six male college students were individually exposed to a standardized provocative test in a slow rotation room after six apparently identical treatments comprising four placebos and two medications. Efficacy was categorized as beneficial, inconsequential, or detrimental. None of the responses was detrimental. Following the first administration of the therapeutic system, there were four beneficial responses after 12 h but none was beneficial after 72 h. Following the second treatment regimen, there were four beneficial responses after 12 h and three beneficial responses after 72 h. Great individual differences were demonstrated, two subjects accounting for six beneficial responses and two accounting for only one beneficial response. The difference in efficacy after 12 and 72 h has practical and theoretical significance.

  14. 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

    ... 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 contained in Atropa belladonna and Datura stramonium have been present as ingredients in cough-cold...

  15. In Vitro Acaricidal Activity of Atropa belladonna and Its Components, Scopolamine and Atropine, against Rhipicephalus (Boophilus) microplus

    PubMed Central

    Godara, R.; Katoch, M.; Yadav, Anish; Parveen, S.; Vij, Bhavna; Khajuria, Varun; Singh, G.; Singh, Nirbhay K.

    2014-01-01

    In vitro efficacy of methanolic extract of Atropa belladonna and its components scopolamine and atropine was assessed against Rhipicephalus (Boophilus) microplus. Five concentrations of the extract (1.25%, 2.5%, 5%, 10%, and 20%) were used whereas scopolamine and atropine were each tested at 0.1%. In adult immersion test, the extract was lethal to ticks at 20% concentration. The LC50 and LC95 values were determined as 6.875% and 17.306%, respectively. The extract caused a significant reduction (P < 0.05) in egg mass production at 10% concentration. In larval packet test, the extract was lethal to larvae in the concentrations of 10% and 20% after 24 h, with LC50 and LC95 values of 1.321% and 4.935%, respectively. Scopolamine and atropine showed 93.3% and 60.0% mortality of adult ticks, respectively, but they caused complete (100%) blocking of hatching as well as 100% larval mortality. Scopolamine and atropine were observed to be more potent than the crude extract at an equivalent concentration in both the bioassays. PMID:25516877

  16. In vitro acaricidal activity of Atropa belladonna and its components, scopolamine and atropine, against Rhipicephalus (Boophilus) microplus.

    PubMed

    Godara, R; Katoch, M; Katoch, R; Yadav, Anish; Parveen, S; Vij, Bhavna; Khajuria, Varun; Singh, G; Singh, Nirbhay K

    2014-01-01

    In vitro efficacy of methanolic extract of Atropa belladonna and its components scopolamine and atropine was assessed against Rhipicephalus (Boophilus) microplus. Five concentrations of the extract (1.25%, 2.5%, 5%, 10%, and 20%) were used whereas scopolamine and atropine were each tested at 0.1%. In adult immersion test, the extract was lethal to ticks at 20% concentration. The LC50 and LC95 values were determined as 6.875% and 17.306%, respectively. The extract caused a significant reduction (P < 0.05) in egg mass production at 10% concentration. In larval packet test, the extract was lethal to larvae in the concentrations of 10% and 20% after 24 h, with LC50 and LC95 values of 1.321% and 4.935%, respectively. Scopolamine and atropine showed 93.3% and 60.0% mortality of adult ticks, respectively, but they caused complete (100%) blocking of hatching as well as 100% larval mortality. Scopolamine and atropine were observed to be more potent than the crude extract at an equivalent concentration in both the bioassays.

  17. In vitro acaricidal activity of Atropa belladonna and its components, scopolamine and atropine, against Rhipicephalus (Boophilus) microplus.

    PubMed

    Godara, R; Katoch, M; Katoch, R; Yadav, Anish; Parveen, S; Vij, Bhavna; Khajuria, Varun; Singh, G; Singh, Nirbhay K

    2014-01-01

    In vitro efficacy of methanolic extract of Atropa belladonna and its components scopolamine and atropine was assessed against Rhipicephalus (Boophilus) microplus. Five concentrations of the extract (1.25%, 2.5%, 5%, 10%, and 20%) were used whereas scopolamine and atropine were each tested at 0.1%. In adult immersion test, the extract was lethal to ticks at 20% concentration. The LC50 and LC95 values were determined as 6.875% and 17.306%, respectively. The extract caused a significant reduction (P < 0.05) in egg mass production at 10% concentration. In larval packet test, the extract was lethal to larvae in the concentrations of 10% and 20% after 24 h, with LC50 and LC95 values of 1.321% and 4.935%, respectively. Scopolamine and atropine showed 93.3% and 60.0% mortality of adult ticks, respectively, but they caused complete (100%) blocking of hatching as well as 100% larval mortality. Scopolamine and atropine were observed to be more potent than the crude extract at an equivalent concentration in both the bioassays. PMID:25516877

  18. Pretreatment with 5-hydroxymethyl-2-furaldehyde blocks scopolamine-induced learning deficit in contextual and spatial memory in male mice.

    PubMed

    Lee, Younghwan; Gao, Qingtao; Kim, Eunji; Lee, Younghwa; Park, Se Jin; Lee, Hyung Eun; Jang, Dae Sik; Ryu, Jong Hoon

    2015-07-01

    5-Hydroxymethyl-2-furaldehyde (5-HMF) is a compound derived from the dehydration of certain sugars. The aim of the present study was to evaluate the effect of 5-HMF on the cognitive impairment induced by scopolamine, a muscarinic receptor antagonist. To measure various cognitive functions, we conducted the step-through passive avoidance task, the Y-maze task and the Morris water maze task. A single administration of 5-HMF (5 or 10mg/kg, p.o.) significantly attenuates scopolamine-induced cognitive impairment in these behavioral tasks without changes in locomotor activity, and the effect of 5-HMF on scopolamine-induced cognitive impairment was significantly reversed by a sub-effective dose of MK-801, an NMDA receptor antagonist. In addition, a single administration of 5-HMF (10mg/kg, p.o.) enhanced the cognitive performance of normal naïve mice in the passive avoidance task. Furthermore, Western blot analysis revealed that the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II-α (CaMKII) and extracellular signal-regulated kinases (ERK) were significantly enhanced by the single administration of 5-HMF in the hippocampal tissues. Taken together, the present study suggests that 5-HMF may block scopolamine-induced learning deficit and enhance cognitive function via the activation of NMDA receptor signaling, including CaMKII and ERK, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease.

  19. P7C3 Attenuates the Scopolamine-Induced Memory Impairments in C57BL/6J Mice.

    PubMed

    Jiang, Bo; Song, Lu; Huang, Chao; Zhang, Wei

    2016-05-01

    Memory impairment is the most common symptom in patients with Alzheimer's disease. The purpose of this study is to evaluate the memory enhancing effects of P7C3, a recently identified compound with robust proneurogenic and neuroprotective effects, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. Different behavior tests including the Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. Scopolamine significantly decreased the spontaneous alternation and step-through latency of C57BL/6J mice in Y-maze test and passive avoidance test, whereas increased the time of mice spent to find the hidden platform in Morris water maze test. Importantly, intraperitoneal administration of P7C3 effectively reversed those Scopolamine-induced cognitive impairments in C57BL/6J mice. Furthermore, P7C3 treatment significantly enhanced the level of brain-derived neurotrophic factor (BDNF) signaling pathway in the cortex and hippocampus, and the usage of selective BDNF signaling inhibitor fully blocked the anti-amnesic effects of P7C3. Therefore, these findings suggest that P7C3 could improve the scopolamine-induced learning and memory impairment possibly through activation of BDNF signaling pathway, thereby exhibiting a cognition-enhancing potential.

  20. Theory of antimotion sickness drug mechanisms.

    NASA Technical Reports Server (NTRS)

    Wood, D. C.; Graybiel, A.

    1972-01-01

    The results of a series of antimotion sickness drug evaluations indicates that drugs with central anticholinergic actions and drugs that increase central sympathetic activity are effective against motion sickness. The combination of these actions produces a synergistic effect against motion sickness. The effect of these medications on central acetylcholine or on norepinephrine could alter a balance between the neurons in the vestibular and reticular areas which influence motion sickness and also sympathetic and parasympathetic reactions. It is suggested that this could be their mechanism of action in preventing motion sickness.

  1. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    SciTech Connect

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A.

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ► PHY attenuated GD-induced seizure development, but not seizure duration.

  2. The role of the central cholinergic projections in cognition: implications of the effects of scopolamine on discrimination learning by monkeys.

    PubMed

    Harder, J A; Baker, H F; Ridley, R M

    1998-01-01

    In humans, administration of the cholinergic antagonist scopolamine impairs the encoding of information into long-term memory and has effects on other cognitive processes. It has been supposed that it is inhibition of the rising cholinergic projections from the basal forebrain, specifically from the basal nucleus of Meynert (NBM) to the neocortex and from the medial septum/vertical limb of the diagonal band of Broca (MS/VDB) to the hippocampus, that results in these cognitive impairments. In this paper, we describe the effects of scopolamine treatment in monkeys on learning different sorts of visual discrimination and visuospatial conditional tasks and compare these results to the effects of lesions of the rising cholinergic projections. Experiments in rodents in which these projections have been selectively destroyed have failed to produce a consensus view of the functions of these two areas. In particular, highly specific immunotoxic lesions of the NBM have largely failed to produce changes in task performance that can be interpreted as resulting from a cognitive impairment. In monkeys, lesions of the NBM produce modest or short-lasting, impairments in visual discrimination learning, retention, and reversal, whereas lesions of the MS/VDB produce large and permanent impairments of certain types of conditional learning. Similar impairments produced by scopolamine in monkeys and additive effects of lesions of the NBM or MS/VDB with scopolamine suggest that scopolamine has these effects by acting on the rising cholinergic pathways rather than on other cholinergic systems in the brain. It is argued that the rising cholinergic projections sustain the functions of the target areas; in the case of the hippocampus in humans, the function is usually regarded as being the analysis of information in a way that is pertinent to the formation of episodic memories and in the case of the neocortex, is the analysis of information in a manner that is relevant to the cognitive

  3. Side effects of antimotion sickness drugs

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

    The effects on operational proficiency of the antimotion sickness drugs scopolamine, promethazine and d-amphetamine are tested using a computerized pursuit meter. Proficiency is not significantly affected by oral doses of 0.25 mg or 0.50 mg scopolamine but is descreased by oral or I.M. doses of 25 mg promethazine. The performance decrement associated with 25 mg oral promethazine is prevented when combined with 10 mg oral d-amphetamine. The combination of 25 mg I.M. promethazine, 25 mg oral promethazine and 10 mg d-amphetamine produces less performance decrement than oral or I.M. doses of promethazine alone, though more performance decrement than a placebo. I.M. promethazine is adsorbed slowly and consequently may provoke drowsiness.

  4. [Emergent drugs (III): hallucinogenic plants and mushrooms].

    PubMed

    Burillo-Putze, G; López Briz, E; Climent Díaz, B; Munné Mas, P; Nogue Xarau, S; Pinillos, M A; Hoffman, R S

    2013-01-01

    An increase in the consumption of vegetable substances with a hallucinogenic effect has been observed. Some of these substances are associated with ancestral religious ceremonies, while many of them are legal or are partially regulated. Salvia divinorum is a powerful kappa receptor agonist, with dissociative and hallucinogenic properties, which start quickly and have a short duration. Kratom (Mytragyna speciosa) has mitragynine as its principal alkaloid, with stimulating effects at low doses (coke-like effect), and sedative effects (opiate-like effect) at high doses. Several deaths from its consumption have been detected. The consumption of hallucinogenic mushrooms appears in cyclic form, although there has been increase in their online offer. They are consumed in search of their hallucinogenic effects, above all those belonging to the family of psilocybes, which contain tryptamines with a hallucinogenic effect similar to LSD. Peyote (Lophophora psilocybes), a cactus rich in mescaline (trimetoxifeniletilamina), produces hallucinations of the five senses, and forms part of the religious culture of the North American Indians. Daturas, which are ubiquitous, produce anticholinergic symptoms and effects on the central nervous system (delirium, hallucinations, etc.), due to their high atropine and scopolamine content. Other substances used for their hallucinogenic effects include the drink known as ayahuasca, and seeds for preparing infusions like Ololiuqui, Morning Glory (Ipomoea violacea), Hawaian Baby Woodrose (Argyreia nervosa), Syrian Rue (Peganum harmala) and Iboga Rootbark (Tabernanthe iboga). PMID:24406363

  5. [Emergent drugs (III): hallucinogenic plants and mushrooms].

    PubMed

    Burillo-Putze, G; López Briz, E; Climent Díaz, B; Munné Mas, P; Nogue Xarau, S; Pinillos, M A; Hoffman, R S

    2013-01-01

    An increase in the consumption of vegetable substances with a hallucinogenic effect has been observed. Some of these substances are associated with ancestral religious ceremonies, while many of them are legal or are partially regulated. Salvia divinorum is a powerful kappa receptor agonist, with dissociative and hallucinogenic properties, which start quickly and have a short duration. Kratom (Mytragyna speciosa) has mitragynine as its principal alkaloid, with stimulating effects at low doses (coke-like effect), and sedative effects (opiate-like effect) at high doses. Several deaths from its consumption have been detected. The consumption of hallucinogenic mushrooms appears in cyclic form, although there has been increase in their online offer. They are consumed in search of their hallucinogenic effects, above all those belonging to the family of psilocybes, which contain tryptamines with a hallucinogenic effect similar to LSD. Peyote (Lophophora psilocybes), a cactus rich in mescaline (trimetoxifeniletilamina), produces hallucinations of the five senses, and forms part of the religious culture of the North American Indians. Daturas, which are ubiquitous, produce anticholinergic symptoms and effects on the central nervous system (delirium, hallucinations, etc.), due to their high atropine and scopolamine content. Other substances used for their hallucinogenic effects include the drink known as ayahuasca, and seeds for preparing infusions like Ololiuqui, Morning Glory (Ipomoea violacea), Hawaian Baby Woodrose (Argyreia nervosa), Syrian Rue (Peganum harmala) and Iboga Rootbark (Tabernanthe iboga).

  6. Inhalation delivery of asthma drugs.

    PubMed

    Matthys, H

    1990-01-01

    In the immediate future, metered-dose inhalers (MDIs) with spacers remain the aerosol application of choice for topical steroids, mainly to reduce side effects. For beta 2-agonist, anticholinergics and prophylactic drugs, MDI (with or without demand valve), dry powder inhalers (multidose inhalers), ultrasonic or jet aerosol generators (with or without mechanical breathing assistance [IPPB]) are chosen according to the preference or the ability of the patients to perform the necessary breathing maneuvers as well as the availability of different products in different countries.

  7. Functional identification of hyoscyamine 6β-hydroxylase from Anisodus acutangulus and overproduction of scopolamine in genetically-engineered Escherichia coli.

    PubMed

    Kai, Guoyin; Liu, Yuanyuan; Wang, Xiaoyun; Yang, Sheng; Fu, Xueqing; Luo, Xiuqin; Liao, Pan

    2011-07-01

    Hyoscyamine 6β-hydroxylase (H6H; EC 1.14.11.11) converts hyoscyamine to scopolamine in the last step of scopolamine biosynthetic pathway. The gene encoding H6H in Anisodus acutangulus was cloned and expressed in Escherichia coli and the recombinant proteins fused with His-tag or GST-tag at its N-terminal were purified and then confirmed by Western bolt analysis. The biofunctional assay revealed that the His-AaH6H and GST-AaH6H converted hyoscyamine (40 mg/l) to scopolamine at 32 and 31 mg/l, respectively. This is the first report on AaH6H expression, purification and functional characterization facilitates further genetic improvement of scopolamine yield in A. acutangulus.

  8. Cognitive enhancing and antioxidant activity of ethyl acetate soluble fraction of the methanol extract of Hibiscus rosa sinensis in scopolamine-induced amnesia

    PubMed Central

    Nade, Vandana S.; Kanhere, Sampat V.; Kawale, Laxman A.; Yadav, Adhikrao V.

    2011-01-01

    Objective: The objective of the present study was to evaluate the cognitive enhancing and antioxidant activity of Hibiscus rosa sinensis. Materials and Methods: The learning and memory was impaired by administration of scopolamine (1 mg/kg, i.p.) in mice which is associated with altered brain oxidative status. The object recognition test (ORT) and passive avoidance test (PAT) were used to assess cognitive enhancing activity. Animals were treated with an ethyl acetate soluble fraction of the methanol extract of H. sinensis (25, 50 and 100 mg/kg, p.o). Results: The ethyl acetate soluble fraction of the methanol extract of H. sinensis (EASF) attenuated amnesia induced by scopolamine and aging. The discrimination index (DI) was significantly decreased in the aged and scopolamine group in ORT. Pretreatment with EASF significantly increased the DI. In PAT, scopolamine-treated mice exhibited significantly shorter step-down latencies (SDL). EASF treatment showed a significant increase in SDL in young, aged as well as in scopolamine-treated animals. The biochemical analysis of brain revealed that scopolamine treatment increased lipid peroxidation and decreased levels of superoxide dismutase (SOD) and glutathione reductase (GSH). Administration of extract significantly reduced LPO and reversed the decrease in brain SOD and GSH levels. The administration of H. sinensis improved memory in amnesic mice and prevented the oxidative stress associated with scopolamine. The mechanism of such protection of H. sinensis may be due to augmentation of cellular antioxidants. Conclusion: The results of the present study suggested that H. sinensis had a protective role against age and scopolamine-induced amnesia, indicating its utility in management of cognitive disorders. PMID:21572646

  9. Effects of lavender oil inhalation on improving scopolamine-induced spatial memory impairment in laboratory rats.

    PubMed

    Hritcu, Lucian; Cioanca, Oana; Hancianu, Monica

    2012-04-15

    Lavender is reported to be an effective medical plant in treating inflammation, depression, stress and mild anxiety in Europe and the USA. The present study investigated the effects of two different lavender essential oils from Lavandula angustifolia ssp. angustifolia Mill. (Lamiaceae) and Lavandula hybrida Rev. (Lamiaceae) on neurological capacity of male Wistar rats subjected to scopolamine (0.7mg/kg)-induced dementia rat model. Chronic exposures to lavender essential oils (daily, for 7 continuous days) significantly reduced anxiety-like behavior and inhibited depression in elevated plus-maze and forced swimming tests, suggesting anxiolytic and antidepressant activity. Also, spatial memory performance in Y-maze and radial arm-maze tasks was improved, suggesting positive effects on memory formation. Taken together, multiple exposures to lavender essential oils could effectively reverse spatial memory deficits induced by dysfunction of the cholinergic system in the rat brain and might provide an opportunity for management neurological abnormalities in dementia conditions.

  10. Effect of oxotremorine, physostigmine, and scopolamine on brain acetylcholine synthesis: a study using HPLC

    SciTech Connect

    Bertrand, N.; Beley, A. )

    1990-11-01

    The synthesis rate of brain acetylcholine (ACh) was estimated in mice following i.v. administration of ({sup 3}H)choline (Ch). The measurements were performed 1 min after the tracer injection, using the ({sup 3}H)ACh/({sup 3}H)Ch specific radioactivity ratio as an index of ACh synthesis rate. Endogenous and labeled Ch and ACh were quantified using HPLC methodology. Oxotremorine and physostigmine (0.5 mg/kg, i.p.) increased the steady state concentration of brain ACh by + 130% and 84%, respectively and of Ch by + 60% (oxotremorine); they decreased ACh synthesis by 62 and 55%, respectively. By contrast, scopolamine (0.7 mg/kg, i.p.) decreased the cerebral content of Ch by - 26% and of ACh by - 23% without enhancing the synthesis of ACh. The results show the utility of HPLC methodology in the investigation of ACh turnover.

  11. Effects of diazepam, pentobarbital, scopolamine and the timing of saline injection on learned immobility in rats.

    PubMed

    De Pablo, J M; Ortiz-Caro, J; Sanchez-Santed, F; Guillamón, A

    1991-11-01

    The rat forced-swimming test (FST) is widely used for screening substances with a potential antidepressant effect. Rat immobility shown in the FST has been interpreted as "behavioral despair" and has been suggested as an animal model of human depression. In the following series of experiments, it is shown that pentobarbital and scopolamine administered immediately after the first phase, and diazepam administered 15 minutes before the first phase, behave as false positives in the FST. It is concluded that the learning-memory hypothesis seems to cope better with the behavior of rats during the FST than the "behavioral despair" hypothesis. It is also shown that the sensitivity of the FST is affected by the fact that the last saline injection, one hour before the second phase, increases the animals' mobility.

  12. Efficacy study of Prunus amygdalus (almond) nuts in scopolamine-induced amnesia in rats

    PubMed Central

    Kulkarni, Kirti S.; Kasture, S.B.; Mengi, S.A.

    2010-01-01

    Objective: Cognitive disorders such as amnesia, attention deficit and Alzheimer’s disease are emerging nightmares in the field of medicine because no exact cure exists for them, as existing nootropic agents (piractam, tacrine, metrifonate) have several limitations. The present study was undertaken to investigate the effect of Prunus amygdalus (PA) nuts on cognitive functions, total cholesterol levels and cholinesterase (ChE) activity in scopolamine-induced amnesia in rats. Materials and Methods: The paste of PA nuts was administered orally at three doses (150, 300 and 600 mg/kg) for 7 and 14 consecutive days to the respective groups of rats. Piracetam (200 mg/kg) was used as a standard nootropic agent. Learning and memory parameters were evaluated using elevated plus maze (EPM), passive avoidance and motor activity paradigms. Brain ChE activity and serum biochemical parameters like total cholesterol, total triglycerides and glucose were evaluated. Results: It was observed that PA at the above-mentioned doses after 7 and 14 days of administration in the respective groups significantly reversed scopolamine (1 mg/kg i.p.)-induced amnesia, as evidenced by a decrease in the transfer latency in the EPM task and step-down latency in the passive avoidance task. PA reduced the brain ChE activity in rats. PA also exhibited a remarkable cholesterol and triglyceride lowering property and slight increase in glucose levels in the present study. Conclusion: Because diminished cholinergic transmission and increase in cholesterol levels appear to be responsible for the development of amyloid plaques and dementia in Alzheimer patients, PA may prove to be a useful memory-restorative agent. It would be worthwhile to explore the potential of this plant in the management of Alzheimer’s disease. PMID:20871769

  13. Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

    NASA Technical Reports Server (NTRS)

    Singh, Rajendra P.; Daniels, Vernie R.; Crady, Camille J.; Derendorf, H.; Putcha, L.

    2011-01-01

    Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as 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 in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: 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.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  14. Delirium with anticholinergic symptoms after a combination of paliperidone and olanzapine pamoate in a patient known to smoke cannabis: an unfortunate coincidence.

    PubMed

    Kokalj, Anja; Rijavec, Nikolina; Tavčar, Rok

    2016-01-01

    We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone. PMID:27335358

  15. Characterization and agonist regulation of muscarinic ([3H]N-methyl scopolamine) receptors in isolated ventricular myocytes from rat.

    PubMed

    Horackova, M; Robinson, B; Wilkinson, M

    1990-11-01

    Cell surface muscarinic cholinergic receptors have been characterized and quantified for the first time, in intact, isolated adult rat cardiomyocytes. The cells were previously established as functionally fully compatible with cellular responses in intact cardiac tissue. The specific binding of the hydrophilic radioligand, [3H]-NMS, (N-methyl-[3H]-scopolamine methylchloride) was found to be stereo-specific, saturable, reversible and of high affinity. Binding of [3H]-NMS demonstrated appropriate drug specificity and was positively correlated with increasing cell concentrations. Bmax for [3H]-NMS binding to ventricular myocytes, enzymatically dissociated from adult male rats, was 15.8 +/- 1.03 fmol/25 x 10(3) cells (at 4 degrees C) and KD was 0.27 +/- 0.05 nM (n = 14). Binding assays performed at a higher incubation temperature (30 degrees C) yielded a higher Bmax value (22.1 +/- 1.6 fmol/25 x 10(3) cells; n = 11; P less than 0.005 vs. Bmax at 4 degrees C) but an unchanged KD (0.23 +/- 0.06 nM). Pretreatment of myocytes with the muscarinic agonist carbachol (1 mM) at 37 degrees C resulted in a reduction (down-regulation) in specific binding of the hydrophilic ligand [3H]-NMS. The magnitude of this reduction and its rate of recovery were dependent on the time of the exposure to carbachol. Exposures of 30-60 min elicited down-regulated by 35% (Bmax = 14.29 +/- 1.66 changed to 9.5 +/- 1.79 fmol/25 x 10(3) cells, without change in KD P less than 0.01, n = 4). The down-regulation of the muscarinic receptors by carbachol was insensitive to application of bacitracin - an inhibitor of endocytosis. On the other hand preincubation with 10(-9)M atropine, a muscarinic antagonist, hindered the agonist-induced receptor "loss" from the cell surface confirming the muscarinic nature of these receptors. We conclude that our preparation of intact, isolated ventricular cardiomyocytes is ideally suited for the study of cell surface muscarinic receptor regulation under physiological and

  16. Characterization and agonist regulation of muscarinic ([3H]N-methyl scopolamine) receptors in isolated ventricular myocytes from rat.

    PubMed

    Horackova, M; Robinson, B; Wilkinson, M

    1990-11-01

    Cell surface muscarinic cholinergic receptors have been characterized and quantified for the first time, in intact, isolated adult rat cardiomyocytes. The cells were previously established as functionally fully compatible with cellular responses in intact cardiac tissue. The specific binding of the hydrophilic radioligand, [3H]-NMS, (N-methyl-[3H]-scopolamine methylchloride) was found to be stereo-specific, saturable, reversible and of high affinity. Binding of [3H]-NMS demonstrated appropriate drug specificity and was positively correlated with increasing cell concentrations. Bmax for [3H]-NMS binding to ventricular myocytes, enzymatically dissociated from adult male rats, was 15.8 +/- 1.03 fmol/25 x 10(3) cells (at 4 degrees C) and KD was 0.27 +/- 0.05 nM (n = 14). Binding assays performed at a higher incubation temperature (30 degrees C) yielded a higher Bmax value (22.1 +/- 1.6 fmol/25 x 10(3) cells; n = 11; P less than 0.005 vs. Bmax at 4 degrees C) but an unchanged KD (0.23 +/- 0.06 nM). Pretreatment of myocytes with the muscarinic agonist carbachol (1 mM) at 37 degrees C resulted in a reduction (down-regulation) in specific binding of the hydrophilic ligand [3H]-NMS. The magnitude of this reduction and its rate of recovery were dependent on the time of the exposure to carbachol. Exposures of 30-60 min elicited down-regulated by 35% (Bmax = 14.29 +/- 1.66 changed to 9.5 +/- 1.79 fmol/25 x 10(3) cells, without change in KD P less than 0.01, n = 4). The down-regulation of the muscarinic receptors by carbachol was insensitive to application of bacitracin - an inhibitor of endocytosis. On the other hand preincubation with 10(-9)M atropine, a muscarinic antagonist, hindered the agonist-induced receptor "loss" from the cell surface confirming the muscarinic nature of these receptors. We conclude that our preparation of intact, isolated ventricular cardiomyocytes is ideally suited for the study of cell surface muscarinic receptor regulation under physiological and

  17. [Drug-induced Cognitive Impairment].

    PubMed

    Shinohara, Moeko; Yamada, Masahito

    2016-04-01

    Elderly people are more likely than young people to develop cognitive impairments associated with medication use. One of the reasons for this is that renal and liver functions are often impaired in elderly people. Dementia and delirium (an acute confused state) are known to be associated with drug toxicity. Anticholinergic medications are common causes of both acute and chronic cognitive impairment. Psychoactive drugs, antidepressants and anticonvulsants can cause dementia and delirium. In addition, non-psychoactive drugs such as histamine H2 receptor antagonists, corticosteroids, NSAIDs (nonsteroidal anti-inflammatory agent), and cardiac medications, may cause acute or chronic cognitive impairment. Early diagnosis and withdrawal of the offending agent are essential for the prevention of drug-induced dementia and delirium. PMID:27056860

  18. The effects of daidzin and its aglycon, daidzein, on the scopolamine-induced memory impairment in male mice.

    PubMed

    Kim, Dong Hyun; Jung, Hyun Ah; Park, Se Jin; Kim, Jong Min; Lee, Seungjoo; Choi, Jae Su; Cheong, Jae Hoon; Ko, Kwang Ho; Ryu, Jong Hoon

    2010-10-01

    In this study, the effect of daidzin or daidzein isolated from Pueraria lobata on the memory impairments induced by scopolamine was assessed in male mice using the passive avoidance and the Morris water maze tasks. Administration of daidzin (5 mg/kg) or daidzein (5 mg/kg) significantly reversed the scopolamine (1 mg/kg)-induced cognitive impairments in male mice as evidenced by the passive avoidance test (p < 0.05) and on the Morris water maze test (p < 0.05). Moreover, the ameliorating effects of daidzin or daidzein were antagonized by tamoxifen (1 mg/kg), the nonspecific estrogen receptor antagonist. These results indicate that daidzin or daidzein may be useful in cognitive impairment induced by cholinergic dysfunction, and this beneficial effect is mediated, in part, via estrogen receptor.

  19. Memory-improving activity of Melissa officinalis extract in naïve and scopolamine-treated rats.

    PubMed

    Soodi, M; Naghdi, N; Hajimehdipoor, H; Choopani, S; Sahraei, E

    2014-01-01

    Melissa officinalis L. (Labiatae) traditionally used in treating neurological disorders has also been identified as a memory-enhancing herb. The extract of M. officinalis has a cholinergic property. The role of basal forebrain cholinergic neurons, the neurons that are destroyed in Alzheimer's disease (AD), in learning and memory, is also well known. The aim of this study is to investigate the role of cholinergic system on the memory improving activity of M. officinalis extract. The leaves of M. officinalis were extracted with ethanol 80% using the maceration method. Rats received intra-peritoneal injections of M. officinalis extract in different doses (50-400 mg/kg) alone or in combination with scopolamine (1 mg/kg) before being trained in a Morris water maze (MWM) in a single-day training protocol. After training, the acetylcholinesterase enzyme (AChE) activity was measured in the hippocampus. Administration of M. officinalis extract (200 mg/kg) could significantly enhance learning and memory of naïve rats (p<0.001) and significantly ameliorate scopolamine-induced learning deficit, but the effect of the extract was not dose dependent, and doses above 200 mg/kg could neither enhance memory in naïve rats nor reverse scopolamine-induced memory impairment. Also, inhibition of AChE activity was observed in both naïve and scopolamine-induced memory-impaired rats. These results suggest that M. officinalis can improve memory and that the cholinergic property of the extract may contribute to the memory-improving effects observed in this study. Then M. officinalis extract has potential therapeutic value in alleviating certain memory impairment observed in AD.

  20. Prefrontal Gray Matter Morphology Mediates the Association Between Serum Anticholinergicity and Cognitive Functioning in Early Course Schizophrenia

    PubMed Central

    Wojtalik, Jessica A.; Eack, Shaun M.; Pollock, Bruce G.; Keshavan, Matcheri S.

    2012-01-01

    Antipsychotic and other medications used in the treatment of schizophrenia place a burden on the cholinergic subsystems of the brain, which have been associated with increased cognitive impairment in the disorder. This study sought to examine the neurobiologic correlates of the association between serum anticholinergic activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive performance on measures of memory and executive function, structural magnetic resonance imaging (MRI) scans, and SAA assays were collected from 47 early course, stabilized outpatients with schizophrenia or schizoaffective disorder. Voxel-based morphometry analyses employing general linear models, adjusting for demographic and illness-related confounds, were used to investigate the associations between SAA, gray matter morphology, and neurocognitive impairment. SAA was related to working memory and executive function impairments. Higher SAA was significantly associated with lower gray matter density in broad regions of the frontal and medial-temporal lobes, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, and striatum. Lower gray matter volume in the left DLPFC was found to significantly mediate the association between SAA and working memory impairment. Disease and/or medication-related cholinergic dysfunction may be associated with brain volume abnormalities in early course schizophrenia, which may account for the association between SAA and cognitive dysfunction in the disorder. PMID:23158779

  1. Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice.

    PubMed

    Kwon, Seung-Hwan; Ma, Shi-Xun; Joo, Hyun-Joong; Lee, Seok-Yong; Jang, Choon-Gon

    2013-11-01

    Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.

  2. Effects of histamine H3 receptor agonists and antagonists on cognitive performance and scopolamine-induced amnesia.

    PubMed

    Giovannini, M G; Bartolini, L; Bacciottini, L; Greco, L; Blandina, P

    1999-10-01

    In previous research we found that pre-training administration of histamine H3 receptor agonists such as (R)-alpha-methylhistamine and imetit impaired rat performance in object recognition and a passive avoidance response at the same doses at which they inhibited the release of cortical acetylcholine in vivo. Conversely, in the present study we report that the post-training administration of (R)-alpha-methylhistamine and imetit failed to affect rat performance in object recognition and a passive avoidance response, suggesting that H3 receptor influences the acquisition and not the recall processes. We also investigated the effects of two H3 receptor antagonists, thioperamide and clobenpropit, in the same behavioral tasks. Pre-training administration of thioperamide and clobenpropit failed to exhibit any procognitive effects in normal animals but prevented scopolamine-induced amnesia. However, also post-training administration of thioperamide prevented scopolamine-induced amnesia. Hence, the ameliorating effects of scopolamine-induced amnesia by H3 receptor antagonism are not only mediated by relieving the inhibitory action of cortical H3 receptors, but other mechanisms are also involved. Nevertheless, H3 receptor antagonists may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

  3. The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats.

    PubMed

    Foley, Andrew G; Murphy, Keith J; Hirst, Warren D; Gallagher, Helen C; Hagan, Jim J; Upton, Neil; Walsh, Frank S; Regan, Ciaran M

    2004-01-01

    The highly potent and selective 5-HT(6) receptor antagonist SB-271046 [5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide] has previously been demonstrated to improve retention significantly in a spatial water maze paradigm in adult rats. However, SB-271046 did not have any effect on task acquisition. As these apparently contradictory findings may be reconciled by a prime influence of SB-271046 on memory consolidation, the ability of this compound to reverse the discrete temporal action of a cholinergic antagonist in the 6-h period following passive avoidance training was investigated. SB-271046, given orally, by gavage, 30 min prior to training Wistar rats in a step-through, light-dark passive avoidance task, was found to reverse significantly the amnesia produced by administering scopolamine (0.8 mg/kg, intraperitoneal) in the 6-h post-training period. The effect was dose-dependent over a range of 3-20 mg/kg. Further, we investigated the cognition-enhancing effects of chronic SB-271046 administration (10 or 20 mg/kg/day; 40 days) on the acquisition and consolidation of a water maze spatial learning task in a population of 20-month-old Wistar rats with age-related learning deficits. Drug treatment progressively and significantly decreased platform swim angle and escape latencies over the five sequential trials on four consecutive daily sessions compared to vehicle-treated controls. SB-271046 also improved task recall as measured by significant increases in the searching of the target quadrant on post-training days 1 and 3, when the animals would have been substantially drug-free. This significant improvement of task recall suggests SB-271046, in addition to inducing symptomatic cognition-enhancing actions, also attenuates age-related decline in neural function.

  4. Effect of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine as evaluated by step-through avoidance response in rats.

    PubMed

    Yu, Chaoyang; Shen, Yao; Xu, Lisha; Zhu, Yuanyuan; Zhuge, Zhenbin; Huang, Yuwen; Henk, Timmerman; Rob, Leurs; Wei, Erqing; Chen, Zhong

    2006-04-15

    In the present study, the effects of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine were investigated as evaluated by step-through avoidance response in adult male rats. Bilateral ventral hippocampal injection of scopolamine (i.h., 2, 5 microg/site) significantly produced depressant effects on the active avoidance response in a dose-dependent manner. Histamine H(3)-antagonist clobenpropit (5, 10 microg/site) significantly ameliorated the fear memory deficits induced by scopolamine in a dose-dependent manner. Its procognitive effect was completely antagonized by immepip (10 microg/site), a selective histamine H(3)-agonist. Both histamine H(1)-antagonist pyrilamine and H(2)-antagonist cimetidine, also inhibited the procognitive effects of clobenpropit. Additionally, the procognitive effects of clobenpropit on the fear memory deficits induced by scopolamine were significantly potentiated by intraperitoneal (i.p.) injection of histidine, a precursor of histamine, but markedly reversed by i.h. injection of alpha-fluoromethylhistidine (FMH, 10 microg/site), a selective and potent histidine decarboxylase inhibitor. It is concluded that the increased endogenous histamine release in the ventral hippocampus ameliorates the scopolamine-induced fear memory deficits, and its action is mainly mediated by histamine presynaptic H(3)-receptors and postsynaptic H(1)- and H(2)-receptors.

  5. Protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments in ovariectomized rats

    PubMed Central

    Hejazian, Seyed Hassan; Karimi, Sareh; Hosseini, Mahmoud; Mousavi, Seyed Mojtaba; Soukhtanloo, Mohammad

    2016-01-01

    Background: Regarding the anti-oxidative effects on the central nervous system, the possible protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments was investigated in ovariectomized (OVX) rats. Materials and Methods: The OVX rats treated by (1) vehicle, (2) scopolamine, and (3–4) scopolamine plus estradiol (20 or 20 or 60 μg/kg). Estradiol was administered (20 or 60 μg/kg, intraperitoneally) daily for 6 weeks after ovariectomy. The rats were examined for learning and memory using passive avoidance test. Scopolamine (2 mg/kg) was injected 30 min after training in the test. The brains were then removed to determine malondialdehyde (MDA) and thiol contents. Results: Scopolamine shortened the time latency to enter the dark compartment in (P < 0.01). Compared to scopolamine, pretreatment by both doses of estradiol prolonged the latency to enter the dark compartment (P < 0.01). The brain tissues MDA concentration as an index of lipid peroxidation was decreased (P < 0.05). Pretreatment by estradiol lowered the concentration of MDA, while it increased thiol content compared to scopolamine (P < 0.05 and P < 0.01). Conclusions: These results allow us to suggest a protection against brain tissues oxidative damage as a possible mechanism for improving effects of low doses of estradiol on scopolamine-induced learning and memory impairments in OVX rats. PMID:27563633

  6. Efficacy comparison of scopolamine (SCP) and diazepam (DZ) against soman-induced lethality in guinea pigs

    SciTech Connect

    Harris, L.W.; Gennings, C.; Carter, W.H.; Anderson, D.R.; Lennox, W.J.

    1994-12-31

    Diazepam (DZ) and scopolamine (SCP) are known to be beneficial when each is used in combination with atropine (AT) + oxime therapy against intoxication by soman, but the efficacy of each might be expected to vary with the dosage of AT. Thus, the therapeutic efficacy of SCP (5 doses; 0 - 0.86 mg/kg) versus DZ (5 doses; 0 - 5 mg/kg), when used in conjunction with AT (3 doses; 0.5 - S mg/kg) + 2-PAM (25 mg/kg) therapy, was tested in groups of pyridostigmine pretreated guinea pigs exposed to 1.6, 2.0, 2.5 or 3.2 LD5Os of soman. Response surface methodology was employed to describe the relationship between lethality and the AT/DZ or AT/SCP dosages. Results show that within the indicated dose ranges used, the efficacy of SCP is not dependent on the presence of AT, whereas AT is needed for DZ to maintain the lowest probability of death. These findings suggest that in guinea pigs SCP could supplement AT or replace DZ as therapy against nerve agent intoxication.

  7. Efficacy comparison of scopolamine and diazepam against soman-induced debilitation in guinea pigs

    SciTech Connect

    Anderson, D.R.; Gennings, C.; Carter, W.H.; Harris, L.W.; Lennox, W.J.

    1994-12-31

    The efficacy of diazepam (DZ) and scopolamine (SCP), in combination with atropine (ATR) + oxime therapy, against soman-induced seizure/convulsive activity and associated brain damage has been demonstrated, but the efficacy of each against the incapacitating effects of soman has not been addressed. Thus, the therapeutic efficacies of SCP (5 doses; 0-0.86 mg/kg) and DZ (5 doses; 0-5 mg/kg), when each was used in conjunction with ATR (3 doses; 0.5-8 mg/kg) + 2-PAM (25 mg/kg) therapy, were compared in groups of pyridostigmine pretreated guinea pigs exposed to 1.6, 2.0, 2.5, or 3.2 LD5Os of soman. Response surface methodology was employed to describe the relationship between soman-induced incapacitation and the ATR/DZ or ATRISCP dosages. Incapacitation was measured by toxicity scores assigned by three graders to test animals at 60 min postsoman. Results show that as the dosage of SCP increased, the mean toxicity scores decreased. Also, within the indicated dose ranges used, the efficacy of SCP was not dependent on the presence of ATR. In contrast, ATR alone was found to be more effective than when combined with DZ at any dose, and indicates that DZ might be temporarily contributing to soman-induced incapacitation. These findings suggest that in guinea pigs, SCP could replace ATR or DZ, or both, as therapy against soman-induced incapacitation.

  8. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System

    PubMed Central

    Xu, Yi-Jun; Yang, Cong; Li, Lin; Hou, Bo-Nan; Chen, Hui-Fang; Wang, Qi

    2016-01-01

    Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction. PMID:27556046

  9. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System.

    PubMed

    Xu, Qing-Qing; Xu, Yi-Jun; Yang, Cong; Tang, Ying; Li, Lin; Cai, Hao-Bin; Hou, Bo-Nan; Chen, Hui-Fang; Wang, Qi; Shi, Xu-Guang; Zhang, Shi-Jie

    2016-01-01

    Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction. PMID:27556046

  10. Amnesia of inhibitory avoidance by scopolamine is overcome by previous open-field exposure

    PubMed Central

    Colettis, Natalia C.; Snitcofsky, Marina; Kornisiuk, Edgar E.; Gonzalez, Emilio N.; Quillfeldt, Jorge 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 open-field (OF) sessions of 3 min each (habituated), behaved as control animals after a weak though over-threshold training in IA. However, after OF exposure, IA LTM was formed and expressed in spite of an extensive or restricted to the hippocampus MAChR blockade. It was reported that during and after OF exposure and reexposure there was an increase in both hippocampal and cortical ACh release that would contribute to “prime the substrate,” e.g., by lowering the synaptic threshold for plasticity, leading to LTM consolidation. In the frame of the “synaptic tagging and capture” hypothesis, plasticity-related proteins synthesized during/after the previous OF could facilitate synaptic plasticity for IA in the same structure. However, IA anterograde amnesia by hippocampal protein synthesis inhibition with anisomycin was also prevented by two OF exposures, strongly suggesting that there would be alternative interpretations for the role of protein synthesis in memory formation and that another structure could also be involved in this “OF effect.” PMID:25322799

  11. β-glucan attenuated scopolamine induced cognitive impairment via hippocampal acetylcholinesterase inhibition in rats.

    PubMed

    Haider, Ali; Inam, Wali; Khan, Shahab Ali; Hifza; Mahmood, Wajahat; Abbas, Ghulam

    2016-08-01

    β-glucan (polysaccharide) rich diet has been reported to enhance cognition in humans but the mechanism remained elusive. Keeping this in mind, the present study was designed to investigate the interaction of β-glucan with central cholinergic system. Briefly, in-silico analysis revealed promising interactions of β-glucan with the catalytic residues of acetylcholinesterase (AChE) enzyme. In line with this outcome, the in vitro assay (Ellman's method) also exhibited inhibition of AChE by β-glucan (IC50=0.68±0.08μg/µl). Furthermore, the in vivo study (Morris water maze) showed significant dose dependent reversal of the amnesic effect of scopolamine (2mg/kg i.p.) by β-glucan treatment (5, 25, 50 and 100mg/kg, i.p.). Finally, the hippocampi of aforementioned treated animals also revealed dose dependent inhibition of AChE enzyme. Hence, it can be deduced that β-glucan possesses potential to enhance central cholinergic tone via inhibiting AChE enzyme. In conclusion, the present study provides mechanistic insight to the cognition enhancing potential of β-glucan. Keeping in mind its dietary use and abundance in nature, it can be considered as economic therapeutic option against cognitive ailments associated with decline in cholinergic neurotransmission.

  12. The modulation by neurosteroids of the scopolamine-induced learning impairment in mice involves an interaction with sigma1 (sigma1) receptors.

    PubMed

    Urani, A; Privat, A; Maurice, T

    1998-07-13

    Neurosteroids have been reported to modulate learning and memory processes in aged animals and in pharmacological models of amnesia. We report here the effects of dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate (PREGS), and progesterone (PROG) on the learning impairment induced in mice by the muscarinic acetylcholine receptor antagonist, scopolamine. Spatial working memory was examined using the spontaneous alternation behavior in a Y-maze and long-term memory using place learning in a rectangular water-maze adapted for mice. Both DHEAS and PREGS (5-20 mg/kg, s.c.) prevented dose-dependently and significantly the scopolamine (2 mg/kg, s.c.)-induced alternation deficits. PROG (2-20 mg/kg, s.c.) failed to affect the scopolamine-induced deficits, but blocked, at 20 mg/kg, the beneficial effects induced by DHEAS or PREGS. In the water-maze, DHEAS (20 mg/kg) attenuated significantly the scopolamine-induced deficits, as observed during the acquisition sessions or the retention test. PROG (2, 20 mg/kg) did not affect the control or scopolamine-treated group performances, but blocked the ameliorating effect of DHEAS. Furthermore, in both tests, the selective sigma1 (sigma1) receptor antagonist NE-100 (1 mg/kg, i.p.) failed to affect the behaviors showed by the control or scopolamine-treated groups, but it blocked the ameliorating effects induced by DHEAS or PREGS. These results confirm the modulating role of neurosteroids in learning and memory processes and demonstrate that their modulation of the cholinergic systems involves an interaction with sigma1 receptors.

  13. Central Anticholinergic Syndrome due to Hypoxia-Induced Bradycardia in a Child with Difficult Intubation Undergoing Complete Dental Restoration: A Case Report.

    PubMed

    Gharavifard, Mohamad; Razavi, Majid; Ghandehari Motlagh, Mehdi; Ziyaeifard, Mohsen

    2014-09-01

    Central anticholinergic syndrome (CAS) following general anesthesia (GA) is a well known syndrome in children and adults. Many cases of CAS have been previously reported in the literature. However, there are only two reports of post resuscitation CAS after administration of small doses of atropine. Hereby, we report a case of CAS in a child undergoing complete dental restoration under GA after receiving a small dose of atropine to reverse hypoxia induced bradycardia. Intraoperative events such as hypoxia or cardiac arrest may play a role as triggers for CAS. However, we cannot establish a causal relationship between the occurrence of CAS and such critical events.

  14. Acute effects of a low-dose atropine/scopolamine mixture as a food contaminant in human volunteers.

    PubMed

    Perharič, Lucija; Juvan, Katja Ažman; Stanovnik, Lovro

    2013-09-01

    To verify the assumptions in our previous risk assessment of an atropine/scopolamine mixture in buckwheat flour, we performed a randomized, double-blind, placebo-controlled cross-over study in 20 healthy, adult volunteers. The volunteers ingested a traditional Slovenian buckwheat meal, made of boiled buckwheat flour to which alkaloids were added. In addition to the placebo they ingested 0.12/0.10, 0.37/0.29, 1.22/0.95, 3.58/2.81 and 12.10/9.50 µg kg(-1) body mass (BM) of the atropine/scopolamine mixture. The changes in body temperature, heart rate, salivary and sweat secretion, pupil size, near-point vision and subjective symptoms were recorded regularly for 4 h after the ingestion. Decreased salivary and sweat secretion, increased heart rate and pupil size and reduced near-point vision accompanied by characteristic subjective symptoms were observed at 12.10/9.50 µg kg(-1) BM. At doses of 0.37/0.29 and 1.22/0.95 µg kg(-1) BM, a significant decrease in the heart rate was noted, which we consider to be a critical effect of a low-dose exposure to the atropine/scopolamine mixture. Although this did not have any clinical relevance in our subjects, it may have serious implications if it occurred in people with pre-existent cardiac conditions or those on medications that may cause bradycardia. No significant changes in the observed end points were noted at 0.12/0.10 µg kg(-1) BM. We estimate that the NOAEL (No Observed Adverse Effect Level) for the atropine/scopolamine mixture lies between the lower two administered doses. Applying the uncertainty factor of 10, we propose a new provisional Acute Reference Doses (ARfDs) of the mixture, i.e. 0.01 µg kg(-1) BM for each alkaloid, and a further refinement using higher-tier approaches.

  15. Novel peptide VIP-TAT with higher affinity for PAC1 inhibited scopolamine induced amnesia.

    PubMed

    Yu, Rongjie; Yang, Yanxu; Cui, Zekai; Zheng, Lijun; Zeng, Zhixing; Zhang, Huahua

    2014-10-01

    A novel peptide VIP-TAT with a cell penetrating peptide TAT at the C-terminus of VIP was constructed and prepared using intein mediated purification with an affinity chitin-binding tag (IMPACT) system to enhance the brain uptake efficiency for the medical application in central nervous system. It was found by labeling VIP-TAT and VIP with fluorescein isothiocyanate (FITC) that the extension with TAT increased the brain uptake efficiency of VIP-TAT significantly. Then short-term and long-term treatment with scopolamine (Scop) was used to evaluate the effect of VIP-TAT or VIP on Scop induced amnesia. Both short-term and long-term administration of VIP-TAT inhibited the latent time reduction in step-through test induced by Scop significantly, but long-term administration of VIP aggravated the Scop induced amnesia. Long-term i.p. injection of VIP-TAT was shown to have positive effect by inhibiting the oxidative damage, apoptosis and the cholinergic system activity reduction that induced by Scop, while VIP exerted negative effect in brain opposite to that in periphery system. The in vitro data showed that VIP-TAT had not only protective but also proliferative effect on Neuro2a cells which was inhibited by PAC1 antagonist PACAP(6-38). Competition binding assay and cAMP assay confirmed that VIP-TAT had higher affinity and activation for PAC1 than VIP. So it was concluded that the significantly stronger protective effect of VIP-TAT against Scop induced amnesia than VIP was due to (1) the enhanced brain uptake efficiency of VIP-TAT and (2) the increased affinity and activation of VIP-TAT for receptor PAC1.

  16. Honokiol improves learning and memory impairments induced by scopolamine in mice.

    PubMed

    Xian, Yan-Fang; Ip, Siu-Po; Mao, Qing-Qiu; Su, Zi-Ren; Chen, Jian-Nan; Lai, Xiao-Ping; Lin, Zhi-Xiu

    2015-08-01

    Honokiol, a lignan isolated from the bark of Magnolia officinalis, has been reported to ameliorate the learning and memory impairments in senesed (SAMP8) mice. However, whether honokiol could improve scopolamine (SCOP)-induced learning and memory deficits in mice is still unknown. In this study, we aimed to investigate whether honokiol could reverse the SCOP-induced learning and memory impairments in mice and to elucidate its underlying mechanisms of action. Mice were given daily intraperitoneal injection of honokiol (10 and 20mg/kg) for 21 consecutive days. The results showed that honokiol significantly improved spatial learning and memory function (as assessed by the Morris water maze test) in the SCOP-treated mice. In addition, treatment with honokiol significantly decreased the protein and mRNA levels of interleukin (IL)-1β and the activity of acetylcholinesterase (AChE), while significantly increased the protein and mRNA levels of IL-10, and the level of acetylcholine (Ach) in the brain of the SCOP-treated mice. Moreover, honokiol also significantly suppressed the production of prostaglandin E 2 (PGE2) and mRNA expression of cyclooxygenase-2 (COX-2) in the brain of the SCOP-treated mice. Mechanistic investigations revealed that honokiol could markedly reverse the amount of phosphorylated Akt and extracellular regulated kinases 1/2 (ERK1/2) changes in the brain of the SCOP-treated mice. These results amply demonstrated that honokiol could improve learning and memory impairments induced by SCOP in mice, and the protective action may be mediated, at least in part, by inhibition of AChE activity, and amelioration of the neuroinflammatory processes in the SCOP-treated mice.

  17. Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro

    PubMed Central

    Lin, Jiajia; Huang, Ling; Yu, Jie; Xiang, Siying; Wang, Jialing; Zhang, Jinrong; Yan, Xiaojun; Cui, Wei; He, Shan; Wang, Qinwen

    2016-01-01

    Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 μM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer’s disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression. PMID:27023569

  18. Comparison of efficacy of ginger with various antimotion sickness drugs

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

    Ginger and several other medications were compared with scopolamine and d-amphetamine for effectiveness in prevention of motion sickness. Methods: Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached. Standardized N.A.S.A. techniques were used for speed of rotation and end-point of motion sickness. Results: The three doses of ginger were all at the placebo level of efficacy. Amitriptyline, ethopropazine and trihexyphenidyl increased the tolerated head movements but the increase was not statistically significant. Significant levels of protection were produced by dimenhydrinate, promethazine, scopolamine and d-amphetamine. Protection was further increased by combination of these latter drugs with d-amphetamine. Efficacy was greatest as the dose was increased. Conclusions: The medication of choice in this study was scopolamine 0.6 mg with d-amphetamine 10 mg. This combination provided good protection with acceptable side effects.

  19. A non-aqueous solid phase extraction method for alkaloid enrichment and its application in the determination of hyoscyamine and scopolamine.

    PubMed

    Long, Zhen; Wang, Chaoran; Guo, Zhimou; Zhang, Xiuli; Nordahl, Lilly; Zeng, Jing; Zeng, Jianguo; Liang, Xinmiao

    2012-03-21

    A non-aqueous solid phase extraction (SPE) method utilizing silica based strong cation exchange (SCX) was developed and optimized for the enrichment of alkaloids. In this method, silica based SCX SPE columns were used for the elimination of non-alkaloid compounds and the preconcentration of alkaloids from the extracts. Mass spectrometry was employed to analyze the alkaloid-enriched fraction, and results showed that the SPE method developed in this study was effective for the removal of non-alkaloids. Then, this pretreatment method was combined with high performance liquid chromatography for the quantification of scopolamine and hyoscyamine from Scopolia tangutica Maxim. The recoveries of scopolamine and (-)-hyoscyamine were 98.51% and 91.12%, respectively. Relative standard deviation values were 1.4% for scopolamine and 1.6% for (-)-hyoscyamine. The linearity was good in the 0.01-0.8 mg mL(-1) range for hyoscyamine and 0.01-0.4 mg mL(-1) range for scopolamine.

  20. Effects of the Methanolic Extract of Vitellaria paradoxa Stem Bark Against Scopolamine-Induced Cognitive Dysfunction and Oxidative Stress in the Rat Hippocampus.

    PubMed

    Foyet, Harquin Simplice; Asongalem, Acha Emmanuel; Oben, Eyong Kenneth; Cioanca, Oana; Hancianu, Monica; Hritcu, Lucian

    2016-10-01

    Vitellaria paradoxa C.F. Gaertn (Sapotaceae) is a perennial three which naturally grows in the northern part of Cameroon. It has been traditionally used in the Cameroonian folk medicine for treating inflammation and pain. In the present study, we evaluate the possible anti-amnesic and antioxidative effects of the methanolic extract of V. paradoxa stem bark in an Alzheimer's disease (AD) rat model of scopolamine. Rats received a single injection of scopolamine (1.5 mg/kg) before behavioral testing and were treated with the methanolic extract (25 and 50 mg/kg), daily, for eight continuous days. Also, the antioxidant activity in the hippocampus was assessed using the total content of reduced glutathione and malondialdehyde levels. The scopolamine-treated rats exhibited the following: decrease of exploratory time and discrimination index within the novel object recognition test, decrease of spontaneous alternations percentage within Y-maze task, and increase of working memory errors, reference memory errors, and time taken to consume all five baits within radial arm-maze task. Administration of the methanolic extract significantly improved these parameters, suggesting positive effects on memory formation processes and antioxidant potential. Our results suggest that the methanolic extract ameliorates scopolamine-induced memory impairment by attenuation of the oxidative stress in the rat hippocampus.

  1. Effects of the Methanolic Extract of Vitellaria paradoxa Stem Bark Against Scopolamine-Induced Cognitive Dysfunction and Oxidative Stress in the Rat Hippocampus.

    PubMed

    Foyet, Harquin Simplice; Asongalem, Acha Emmanuel; Oben, Eyong Kenneth; Cioanca, Oana; Hancianu, Monica; Hritcu, Lucian

    2016-10-01

    Vitellaria paradoxa C.F. Gaertn (Sapotaceae) is a perennial three which naturally grows in the northern part of Cameroon. It has been traditionally used in the Cameroonian folk medicine for treating inflammation and pain. In the present study, we evaluate the possible anti-amnesic and antioxidative effects of the methanolic extract of V. paradoxa stem bark in an Alzheimer's disease (AD) rat model of scopolamine. Rats received a single injection of scopolamine (1.5 mg/kg) before behavioral testing and were treated with the methanolic extract (25 and 50 mg/kg), daily, for eight continuous days. Also, the antioxidant activity in the hippocampus was assessed using the total content of reduced glutathione and malondialdehyde levels. The scopolamine-treated rats exhibited the following: decrease of exploratory time and discrimination index within the novel object recognition test, decrease of spontaneous alternations percentage within Y-maze task, and increase of working memory errors, reference memory errors, and time taken to consume all five baits within radial arm-maze task. Administration of the methanolic extract significantly improved these parameters, suggesting positive effects on memory formation processes and antioxidant potential. Our results suggest that the methanolic extract ameliorates scopolamine-induced memory impairment by attenuation of the oxidative stress in the rat hippocampus. PMID:26620052

  2. The ameliorating effects of 2,3-dihydroxy-4-methoxyacetophenone on scopolamine-induced memory impairment in mice and its neuroprotective activity.

    PubMed

    Weon, Jin Bae; Ko, Hyun-Jeong; Ma, Choong Je

    2013-12-15

    We isolated 2,3-dihydroxy-4-methoxyacetophenone, a neuroprotective compound from Cynenchum paniculatum in our previous study. The present study was conducted to investigate the possible neuroprotective effect of 2,3-dihydroxy-4-methoxyacetophenone that has been previously isolated from Cynenchum paniculatum on hippocampal neuronal cell line, HT22 cells and its possible cognitive-enhancing effect on scopolamine-induced amnesia in mice. Neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells was evaluated by MTT assay. Also, cognitive enhancing effect against scopolamine (1mg/kg, ip) induced learning and memory deficit was measured by Morris water maze test. Oral administered of 2,3-dihydroxy-4-methoxyacetophenone (1, 10, 20, 40 and 50mg/kg) to amnesic mice induced by scopolamine. In Morris water maze test, 2,3-dihydroxy-4-methoxyacetophenone (50mg/kg) improved the impairment of spatial memory induced by scopolamine. 2,3-Dihydroxy-4-methoxyacetophenone protect HT22 cells on glutamate induced cell-death in a dose-dependent manner (EC50 value: 10.94μM). Furthermore, 2,3-dihydroxy-4-methoxyacetophenone was found to inhibit [Ca(2+)] accumulation in HT22 cells and had antioxidantive activity. The results showed that 2,3-dihydroxy-4-methoxyacetophenone exert neuroprotective and cognitive-enhancing activities through its antioxidant activity. We suggest that 2,3-dihydroxy-4-methoxyacetophenone improves cognitive function and may be helpful for the treatment of Alzheimer's disease.

  3. Use of psychotropic drugs and associated dental diseases.

    PubMed

    Fratto, Giovanni; Manzon, Licia

    2014-01-01

    Patients with problems related to central nervous system dysfunctions are often treated with psychotropic drugs. These include antipsychotics, antidepressants, mood stabilizers, anticonvulsants, and drugs blocking specific receptors in the brain such as anticholinergics or beta-blockers. However, these medications have serious side effects affecting the oral health. In addition, many dental patients make use of psychoactive drugs, such as amphetamine, ecstasy, and cocaine. This article aims to review data on the psychotropic drugs being used in the last 30 years, their pharmacological profile, with special attention to the side effects related to the oral health. Oral diseases such as bruxism, orofacial dystonia, oromandibular dyskinesia, and rabbit syndrome are related to extrapyramidal effects of antipsychotic drugs because of their antagonist activity on the dopaminergic receptors. Drugs with anticholinergic and/or antiadrenergic effects such as tricyclic antidepressants may cause dry mouth and related complications such as candidiasis and other oral infections. Among mood stabilizers, lithium treatment induces a wide range of side effects on oral system including dry mouth, sialorrhea, infections, and ulceration of the oral cavity. Psychostimulants may instead provoke xerotomia, gingival enlargements, bruxism, dental erosion, mucosal ulceration, and oral/nasal lesions. This literature review supports the idea that the higher prevalence of oral diseases among patients with mental disorders may be attributed to the side effects of their medications mediated by complex interactions between different targeted receptors. Thus, dentists must be aware of the possible risks of these medications in order to take appropriate precautions in treating these patients. PMID:25492713

  4. Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice.

    PubMed

    Ghumatkar, Priya J; Patil, Sachin P; Jain, Pankaj D; Tambe, Rufi M; Sathaye, Sadhana

    2015-08-01

    Phloretin (PHL), a dihydrochalcone flavonoid usually present in the roots and leaves of apple tree. In vitro study on GT1-7 immortalized hypothalamic neurons exposed to amyloid beta (25-35), demonstrated that PHL significantly influenced membrane fluidity and potential. PHL also significantly decreased excitotoxicity by restoring the calcium homeostasis in the same. Thus, PHL proves to be a promising therapeutic moiety which should be further screened in the treatment of Alzheimer's disease. The objective of the present study was to evaluate the nootropic, neuroprotective and neurotrophic roles of PHL in the subacute scopolamine induced amnesia in mice. In this study, mice were pretreated with PHL 2.5mg/kg, 5mg/kg, 10mg/kg and Donepezil (DON) 1mg/kg intraperitoneally (i.p) for 14days. The last 7days of treatment regimen included daily injection of SCP 1.5mg/kg to induce cognitive deficits. Mice were subjected to behavioral analysis. Biochemical estimation of the brain homogenates for acetylcholinesterase and oxidative stress biomarkers were conducted. Furthermore, immunohistochemical analysis for the brain derived neurotrophic factor (BDNF) was carried out particularly in the hippocampus. PHL was found to significantly improve the performance of mice in Morris water maze test (P<0.001) and significantly decreased the acetylcholinesterase activity (P<0.001) at all doses compared to SCP treated mice. Also, PHL significantly elevated the activity of antioxidant enzymes viz. superoxide dismutase, catalase, reduced glutathione levels (P<0.001) and decreased malonaldehyde levels (P<0.001) in comparison with the SCP group. Immunohistochemistry revealed that PHL treatment dose dependently improved BDNF levels in the hippocampus which were found to be significantly depleted (P<0.001) in the SCP group. Additionally, PHL (10mg/kg) significantly enhanced the spatial memory formation (P<0.05) and neurotrophicity (P<0.001) compared to DON (1mg/kg). The aforementioned research

  5. Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice.

    PubMed

    Ghumatkar, Priya J; Patil, Sachin P; Jain, Pankaj D; Tambe, Rufi M; Sathaye, Sadhana

    2015-08-01

    Phloretin (PHL), a dihydrochalcone flavonoid usually present in the roots and leaves of apple tree. In vitro study on GT1-7 immortalized hypothalamic neurons exposed to amyloid beta (25-35), demonstrated that PHL significantly influenced membrane fluidity and potential. PHL also significantly decreased excitotoxicity by restoring the calcium homeostasis in the same. Thus, PHL proves to be a promising therapeutic moiety which should be further screened in the treatment of Alzheimer's disease. The objective of the present study was to evaluate the nootropic, neuroprotective and neurotrophic roles of PHL in the subacute scopolamine induced amnesia in mice. In this study, mice were pretreated with PHL 2.5mg/kg, 5mg/kg, 10mg/kg and Donepezil (DON) 1mg/kg intraperitoneally (i.p) for 14days. The last 7days of treatment regimen included daily injection of SCP 1.5mg/kg to induce cognitive deficits. Mice were subjected to behavioral analysis. Biochemical estimation of the brain homogenates for acetylcholinesterase and oxidative stress biomarkers were conducted. Furthermore, immunohistochemical analysis for the brain derived neurotrophic factor (BDNF) was carried out particularly in the hippocampus. PHL was found to significantly improve the performance of mice in Morris water maze test (P<0.001) and significantly decreased the acetylcholinesterase activity (P<0.001) at all doses compared to SCP treated mice. Also, PHL significantly elevated the activity of antioxidant enzymes viz. superoxide dismutase, catalase, reduced glutathione levels (P<0.001) and decreased malonaldehyde levels (P<0.001) in comparison with the SCP group. Immunohistochemistry revealed that PHL treatment dose dependently improved BDNF levels in the hippocampus which were found to be significantly depleted (P<0.001) in the SCP group. Additionally, PHL (10mg/kg) significantly enhanced the spatial memory formation (P<0.05) and neurotrophicity (P<0.001) compared to DON (1mg/kg). The aforementioned research

  6. Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

    PubMed Central

    Peña, Ike dela; Yoon, Seo Young; Kim, Hee Jin; Park, Sejin; Hong, Eun Young; Ryu, Jong Hoon; Park, Il Ho; Cheong, Jae Hoon

    2013-01-01

    Background Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results Ginseol k-g3 (25–200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity. PMID:24558303

  7. Combination anticonvulsant treatment of soman-induced seizures.

    PubMed

    Koplovitz, I; Schulz, S; Shutz, M; Railer, R; Macalalag, R; Schons, M; McDonough, J

    2001-12-01

    These studies investigated the effectiveness of combination treatment with a benzodiazepine and an anticholinergic drug against soman-induced seizures. The anticholinergic drugs considered were biperiden, scopolamine, trihexaphenidyl, and procyclidine; the benzodiazepines were diazepam and midazolam. Male guinea pigs were implanted surgically with cortical screw electrodes. Electrocorticograms were displayed continually and recorded on a computerized electroencephalographic system. Pyridostigmine (0.026 mg x kg(-1), i.m.) was injected as a pretreatment to inhibit red blood cell acetylcholinesterase by 30-40%. Thirty minutes after pyridostigmine, 2 x LD50 (56 microg x kg(-1)) of soman was injected s.c., followed 1 min later by i.m. treatment with atropine (2 mg x kg(-1)) + 2-PAM (25 mg x kg(-1)). Electrographic seizures occurred in all animals. Anticonvulsant treatment combinations were administered i.m. at 5 or 40 min after seizure onset. Treatment consisted of diazepam or midazolam plus one of the above-mentioned anticholinergic drugs. All doses of the treatment compounds exhibited little or no antiseizure efficacy when given individually. The combination of a benzodiazepine and an anticholinergic drug was effective in terminating soman-induced seizure, whether given 5 or 40 min after seizure onset. The results suggest a strong synergistic effect of combining benzodiazepines with centrally active anticholinergic drugs and support the concept of using an adjunct to supplement diazepam for the treatment of nerve-agent-induced seizures.

  8. Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition.

    PubMed Central

    Yun, D J; Hashimoto, T; Yamada, Y

    1992-01-01

    The tropane alkaloid scopolamine is a medicinally important anticholinergic drug present in several solanaceous plants. Hyoscyamine 6 beta-hydroxylase (EC 1.14.11.11) catalyzes the oxidative reactions in the biosynthetic pathway leading from hyoscyamine to scopolamine. We introduced the hydroxylase gene from Hyoscyamus niger under the control of the cauliflower mosaic virus 35S promoter into hyoscyamine-rich Atropa belladonna by the use of an Agrobacterium-mediated transformation system. A transgenic plant that constitutively and strongly expressed the transgene was selected, first by screening for kanamycin resistance and then by immunoscreening leaf samples with an antibody specific for the hydroxylase. In the primary transformant and its selfed progeny that inherited the transgene, the alkaloid contents of the leaf and stem were almost exclusively scopolamine. Such metabolically engineered plants should prove useful as breeding materials for obtaining improved medicinal components. Images PMID:1465402

  9. Effects of drugs on mucus clearance.

    PubMed

    Houtmeyers, E; Gosselink, R; Gayan-Ramirez, G; Decramer, M

    1999-08-01

    Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which

  10. Neurophysiological responses to stressful motion and anti-motion sickness drugs as mediated by the limbic system

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Odell, S.

    1982-01-01

    Performance is characterized in terms of attention and memory, categorizing extrinsic mechanism mediated by ACTH, norepinephrine and dopamine, and intrinsic mechanisms as cholinergic. The cholinergic role in memory and performance was viewed from within the limbic system and related to volitional influences of frontal cortical afferents and behavioral responses of hypothalamic and reticular system efferents. The inhibitory influence of the hippocampus on the autonomic and hormonal responses mediated through the hypothalamus, pituitary, and brain stem are correlated with the actions of such anti-motion sickness drugs as scopolamine and amphetamine. These drugs appear to exert their effects on motion sickness symptomatology through diverse though synergistic neurochemical mechanisms involving the septohippocampal pathway and other limbic system structures. The particular impact of the limbic system on an animal's behavioral and hormonal responses to stress is influenced by ACTH, cortisol, scopolamine, and amphetamine.

  11. Effect of polyacetylenes on the neurite outgrowth of neuronal culture cells and scopolamine-induced memory impairment in mice.

    PubMed

    Yamazaki, M; Hirakura, K; Miyaichi, Y; Imakura, K; Kita, M; Chiba, K; Mohri, T

    2001-12-01

    Polyacetylenic alcohols and their linoleates isolated from Panax ginseng C. A. MEYER and Cirsium japonicum DC., of which the lipophilic extracts had been found to affect the neuritogenesis of cultured paraneurons, were demonstrated to have a significant neuritogenic effect on PC12h and Neuro2a cells. Panaxynol and the acetylenic triol in particular were highly efficient at concentrations > or = 2 microm. Panaxynol (20 mg/kg/d, i.p., for 3 d) was confirmed to improve scopolamine-induced memory deficit in mice (Y-maze task). It is suggested that the promotion of neuritogenesis in cultured paraneurons by the addition of panaxynol is related its ability to improve memory deficits in animals.

  12. Improvement of scopolamine-induced memory impairment by Z-ajoene in the water maze in mice.

    PubMed

    Yamada, N; Hattori, A; Hayashi, T; Nishikawa, T; Fukuda, H; Fujino, T

    2004-08-01

    Z-ajoene, a major compound containing sulfur in oil-macerated garlic products, exhibited inhibitory effects against scopolamine-induced memory impairment in mice using the Morris water maze test. The effects of Z-ajoene were observed dose-dependently (0.25-25 mg/kg). At the highest dosage, the memory performance of mice was improved compared to normal mice. The acetylcholinesterase (AChE) activity in the brain was reduced by administration of Z-ajoene dose-dependently. However, alliin and diallyl disulfide, organosulfur compounds from garlic, did not improve memory performance nor AChE inhibitory effect. These results suggest that Z-ajoene may act on the cholinergic system and on memory impairment caused by excess activity of AChE.

  13. Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice.

    PubMed

    Jung, In Ho; Lee, Hyung Eun; Park, Se Jin; Ahn, Young Je; Kwon, Guyoung; Woo, Hyun; Lee, So Young; Kim, Ju Sun; Jo, Yeong-Woo; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

    2014-05-01

    Spinosin is a C-glycoside flavonoid isolated from the seeds of Zizyphus jujuba var. spinosa. This study investigated the effect of spinosin on cholinergic blockade-induced memory impairment in mice. Behavioral tests were conducted using the passive avoidance, Y-maze, and Morris water maze tasks to evaluate the memory-ameliorating effect of spinosin. Spinosin (10 or 20mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in these behavioral tasks with a prolonged latency time in the passive avoidance task, an increased percentage of spontaneous alternation in the Y-maze task and a lengthened swimming time in target quadrant in the Morris water maze task. In addition, a single administration of spinosin in normal naïve mice also enhanced the latency time in the passive avoidance task. To identify the mechanism of the memory-ameliorating effect of spinosin, receptor antagonism analysis and Western blotting were performed. The ameliorating effect of spinosin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose (0.5mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)tetralin, a 5-HT1A receptor agonist. In addition, spinosin significantly increased the expression levels of phosphorylated extracellular signal-regulated kinases and cAMP response element-binding proteins in the hippocampus. Taken together, these results indicate that the memory-ameliorating effect of spinosin may be, in part, due to the serotonergic neurotransmitter system, and that spinosin may be useful for the treatment of cognitive dysfunction in diseases such as Alzheimer's disease.

  14. Comparison of the isolated human and guinea pig gallbladder strip models in the assessment of antispasmodic drugs.

    PubMed

    Baistrocchi, R; de los Santos, A R; Di Girolamo, G; Martí, M L; Pico, J

    1999-12-01

    The objective of this study was to compare the antispasmodic activities of atropine, verapamil, (-)scopolamine n-butyl bromide and propinox in the isolated human and guinea pig gallbladder strip models. Concentration-response curves for each of the agents were obtained in both models following administration of carbachol. Atropine was the only drug to show marked activity in the guinea pig gallbladder model (ED50 = 2.75 x 10(-7) M); the remaining drugs elicited less inhibition of a similar order of magnitude (ED50 = 1.65 x 10(-5), 4.18 x 10(-6) and 2.71 x 10(-5) M for verapamil, [-]scopolamine n-butyl bromide and propinox, respectively). In contrast, results obtained from the human gallbladder strip model revealed differences among the drugs (ED50 = 5.03 x 10(-8), 1.34 x 10(-6), 6.63 x 10(-6) and 5.45 x 10(-5) M for atropine, propinox, verapamil and [-]scopolamine n-butyl bromide, respectively). Based on these results, propinox showed a relative potency in the human gallbladder that was 20.22-fold higher than that in the guinea pig model followed by atropine (5.47-fold) and verapamil (2.49-fold), whereas (-)scopolamine n-butyl bromide was 0.07 times more potent in the guinea pig model. Regression analysis of ED50 values showed a lack of correlation between the two models (r = 0.44). Considering interspecies variations, further studies in human tissues are needed to evaluate the efficacy of antispasmodic drugs.

  15. Human Serial Learning: Enhancement with Arecholine and Choline and Impairment with Scopolamine

    ERIC Educational Resources Information Center

    Sitaram, N.; Weingartner, Herbert

    1978-01-01

    The effects of particular drugs in human memory abilities was examined. The degree of memory enhancement produced by arecholine and choline and the impairment after scopolamaine were inversely proportional to the subject's performance in placebo; that is, "poor" performers were more vulnerable to the drugs than were "good" performers. (Author/CP)

  16. Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert.

    PubMed

    Rispoli, Vincenzo; Rotiroti, Domenicantonio; Carelli, Vincenzo; Liberatore, Felice; Scipione, Luigi; Marra, Rosario; Giorgioni, Gianfabio; Di Stefano, Antonio

    2004-02-19

    The effects of two choline pivaloyl esters, [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium iodide (1) and [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (2), on learning and memory impairments induced in rats by scopolamine or lesions of nucleus basalis magnocellularis (NBM) have been evaluated by object recognition and Morris water maze tests in comparison with Tacrine (THA). Both 1 and 2 restored discrimination in object recognition test for assessing working-episodic memory and improved spatial memory in scopolamine or NBM-lesioned rats as well. The positive effects produced by 1 and 2 on cognitive and memory deficits were well comparable with those evoked by THA, used as reference compound.

  17. [Cloning and expression of the key enzyme hyoscyamine 6 beta-hydroxylase gene (DaH6H) in scopolamine biosynthesis of Datura arborea].

    PubMed

    Qiang, Wei; Hou, Yan-ling; Li, Xiao; Xia, Ke; Liao, Zhi-hua

    2015-10-01

    Hyoscyamine 6 beta-hydroxylase (H6H) is the last rate-limiting enzyme directly catalyzing the formation of scopolamine in tropane alkaloids (TAs) biosynthesis pathway. It is the primary target gene in the genetic modification of TAs metabolic pathway. Full-length cDNA and gDNA sequences of a novel H6H gene were cloned from Datura arborea (DaH6H, GenBank accession numbers for cDNA and gDNA are KR006981 and KR006983, respectively). Nucleotide sequence analysis reveals an open reading frame of 1375 bp encoding 347 amino acids in the cDNA of DaH6H, while the gDNA of DaH6H contains four exons and three introns, with the highest similarity to the gDNA of H6H from D. stramonium. DaH6H also exhibited the most identity of 90.5% with DsH6H in amino acids and harbored conserved 2-oxoglutarate binding motif and two iron binding motifs. The expression level of DaH6H was highest in the mature leaf, followed by the secondary root, and with no expression in the primary root based on qPCR analysis. Its expression was inhibited by MeJA. DaH6H was expressed in E. coli and a 39 kD recombinant protein was detected in SDS-PAGE. Comparison of the contents of scopolamine and hyoscyamine in various TAs-producing plants revealed that D. arborea was one of the rare scopolamine predominant plants. Cloning of DaH6H gene will allow more research in the molecular regulatory mechanism of TAs biosynthesis in distinct plants and provide a new candidate gene for scopolamine metabolic engineering.

  18. Reverse translation of the rodent 5C-CPT reveals that the impaired attention of people with schizophrenia is similar to scopolamine-induced deficits in mice

    PubMed Central

    Young, J W; Geyer, M A; Rissling, A J; Sharp, R F; Eyler, L T; Asgaard, G L; Light, G A

    2013-01-01

    Attentional dysfunction in schizophrenia (SZ) is a core deficit that contributes to multiple cognitive deficits and the resulting functional disability. However, developing procognitive therapeutics for neuropsychiatric disorders have been limited by a ‘translational gap'—a lack of cognitive paradigms having cross-species translational validity and relevance. The present study was designed to perform an initial validation of the cross-species homology of the 5-choice Continuous Performance Test (5C-CPT) in healthy nonpsychiatric comparison subjects (NCS), SZ patients and mice under pharmacologic challenge. The 5C-CPT performance in SZ patients (n=20) was compared with age-matched NCS (n=23). The effects of the general muscarinic receptor antagonist scopolamine on mice (n=21) performing the 5C-CPT were also assessed. SZ subjects exhibited significantly impaired attention in the 5C-CPT, driven by reduced target detection over time and nonsignificantly increased impulsive responding. Similarly, scopolamine significantly impaired attention in mice, driven by reduced target detection and nonsignificantly increased impulsive responding. Scopolamine also negatively affected accuracy and speed of responding in mice, although these measures failed to differentiate SZ vs NCS. Thus, mice treated with scopolamine exhibited similar impairments in vigilance as seen in SZ, although the differences between the behavioral profiles warrant further study. The availability of rodent and human versions of this paradigm provides an opportunity to: (1) investigate the neuroanatomic, neurochemical and genomic architecture of abnormalities in attention observed in clinical populations such as SZ; (2) develop and refine animal models of cognitive impairments; and (3) improve cross-species translational testing for the development of treatments for these impairments. PMID:24217494

  19. Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose 'Liking' and Intake but Scopolamine in Caudal Shell Shifts 'Liking' Toward 'Disgust' and 'Fear'.

    PubMed

    Castro, Daniel C; Terry, Rachel A; Berridge, Kent C

    2016-07-01

    The nucleus accumbens (NAc) contains a hedonic hotspot in the rostral half of medial shell, where opioid agonist microinjections are known to enhance positive hedonic orofacial reactions to the taste of sucrose ('liking' reactions). Within NAc shell, orexin/hypocretin also has been reported to stimulate food intake and is implicated in reward, whereas blockade of muscarinic acetylcholine receptors by scopolamine suppresses intake and may have anti-reward effects. Here, we show that NAc microinjection of orexin-A in medial shell amplifies the hedonic impact of sucrose taste, but only within the same anatomically rostral site, identical to the opioid hotspot. By comparison, at all sites throughout medial shell, orexin microinjections stimulated 'wanting' to eat, as reflected by increases in intake of palatable sweet chocolates. At NAc shell sites outside the hotspot, orexin selectively enhanced 'wanting' to eat without enhancing sweetness 'liking' reactions. In contrast, microinjections of the antagonist scopolamine at all sites in NAc shell suppressed sucrose 'liking' reactions as well as suppressing intake of palatable food. Conversely, scopolamine increased aversive 'disgust' reactions elicited by bitter quinine at all NAc shell sites. Finally, scopolamine microinjections localized to the caudal half of medial shell additionally generated a fear-related anti-predator reaction of defensive treading and burying directed toward the corners of the transparent chamber. Together, these results confirm a rostral hotspot in NAc medial shell as a unique site for orexin induction of hedonic 'liking' enhancement, similar to opioid enhancement. They also reveal distinct roles for orexin and acetylcholine signals in NAc shell for hedonic reactions and motivated behaviors.

  20. [Cloning and expression of the key enzyme hyoscyamine 6 beta-hydroxylase gene (DaH6H) in scopolamine biosynthesis of Datura arborea].

    PubMed

    Qiang, Wei; Hou, Yan-ling; Li, Xiao; Xia, Ke; Liao, Zhi-hua

    2015-10-01

    Hyoscyamine 6 beta-hydroxylase (H6H) is the last rate-limiting enzyme directly catalyzing the formation of scopolamine in tropane alkaloids (TAs) biosynthesis pathway. It is the primary target gene in the genetic modification of TAs metabolic pathway. Full-length cDNA and gDNA sequences of a novel H6H gene were cloned from Datura arborea (DaH6H, GenBank accession numbers for cDNA and gDNA are KR006981 and KR006983, respectively). Nucleotide sequence analysis reveals an open reading frame of 1375 bp encoding 347 amino acids in the cDNA of DaH6H, while the gDNA of DaH6H contains four exons and three introns, with the highest similarity to the gDNA of H6H from D. stramonium. DaH6H also exhibited the most identity of 90.5% with DsH6H in amino acids and harbored conserved 2-oxoglutarate binding motif and two iron binding motifs. The expression level of DaH6H was highest in the mature leaf, followed by the secondary root, and with no expression in the primary root based on qPCR analysis. Its expression was inhibited by MeJA. DaH6H was expressed in E. coli and a 39 kD recombinant protein was detected in SDS-PAGE. Comparison of the contents of scopolamine and hyoscyamine in various TAs-producing plants revealed that D. arborea was one of the rare scopolamine predominant plants. Cloning of DaH6H gene will allow more research in the molecular regulatory mechanism of TAs biosynthesis in distinct plants and provide a new candidate gene for scopolamine metabolic engineering. PMID:26837185

  1. Task- and Treatment Length–Dependent Effects of Vortioxetine on Scopolamine-Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats

    PubMed Central

    Pehrson, Alan L.; Hillhouse, Todd M.; Haddjeri, Nasser; Rovera, Renaud; Porter, Joseph H.; Mørk, Arne; Smagin, Gennady; Song, Dekun; Budac, David; Cajina, Manuel

    2016-01-01

    Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine’s ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine’s effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine’s pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine’s moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine′s cognitive effects, which are observed under chronic dosing conditions in patients with MDD. PMID:27402279

  2. Task- and Treatment Length-Dependent Effects of Vortioxetine on Scopolamine-Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats.

    PubMed

    Pehrson, Alan L; Hillhouse, Todd M; Haddjeri, Nasser; Rovera, Renaud; Porter, Joseph H; Mørk, Arne; Smagin, Gennady; Song, Dekun; Budac, David; Cajina, Manuel; Sanchez, Connie

    2016-09-01

    Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine's ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine's effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine's pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine's moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine's cognitive effects, which are observed under chronic dosing conditions in patients with MDD. PMID:27402279

  3. Simultaneous determination of atropine, anisodamine, and scopolamine in plant extract by nonaqueous capillary electrophoresis coupled with electrochemiluminescence and electrochemistry dual detection.

    PubMed

    Yuan, Baiqing; Zheng, Chunying; Teng, Hong; You, Tianyan

    2010-01-01

    A rapid and simple method was demonstrated for the analysis of atropine, anisodamine, and scopolamine by nonaqueous capillary electrophoresis (NACE) coupled with electrochemiluminescence (ECL) and electrochemistry (EC) dual detection. The mixture of acetonitrile (ACN) and 2-propanol containing 1M acetic acid (HAc), 20mM sodium acetate (NaAc), and 2.5mM tetrabutylammonium perchlorate (TBAP) was used as the electrophoretic buffer. Although a short capillary of 18cm was used, the decoupler was not needed and the separation efficiency was good. The linear ranges of atropine, anisodamine, and scopolamine were 0.5-50, 5-2000, and 50-2000microM, respectively. For six replicate measurements of 100microM scopolamine, 15microM atropine, and 200microM anisodamine, the RSDs of ECL intensity, EC current, and migration time were less than 3.6%, 4.5%, and 0.3%, respectively. In addition, because the organic buffer was used, the working electrode (Pt) was not easily fouled and did not need reactivation. The method was also applied for the determination of these three alkaloids in Flos daturae extract. PMID:19931863

  4. Simple validated LC-MS/MS method for the determination of atropine and scopolamine in plasma for clinical and forensic toxicological purposes.

    PubMed

    Koželj, Gordana; Perharič, Lucija; Stanovnik, Lovro; Prosen, Helena

    2014-08-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of atropine and scopolamine in 100μL human plasma was developed and validated. Sample pretreatment consisted of protein precipitation with acetonitrile followed by a concentration step. Analytes and levobupivacaine (internal standard) were separated on a Zorbax XDB-CN column (75mm×4.6mm i.d., 3.5μm) with gradient elution (purified water, acetonitrile, formic acid). The triple quadrupole MS was operated in ESI positive mode. Matrix effect was estimated for deproteinised plasma samples. Selected reaction monitoring (SRM) was used for quantification in the range of 0.10-50.00ng/mL. Interday precision for both tropanes and intraday precision for atropine was <10%, intraday precision for scopolamine was <14% and <18% at lower limit of quantification (LLOQ). Mean interday and intraday accuracies for atropine were within ±7% and for scopolamine within ±11%. The method can be used for determination of therapeutic and toxic levels of both compounds and has been successfully applied to a study of pharmacodynamic and pharmacokinetic properties of tropanes, where plasma samples of volunteers were collected at fixed time intervals after ingestion of a buckwheat meal, spiked with five low doses of tropanes.

  5. Simultaneous determination of atropine, anisodamine, and scopolamine in plant extract by nonaqueous capillary electrophoresis coupled with electrochemiluminescence and electrochemistry dual detection.

    PubMed

    Yuan, Baiqing; Zheng, Chunying; Teng, Hong; You, Tianyan

    2010-01-01

    A rapid and simple method was demonstrated for the analysis of atropine, anisodamine, and scopolamine by nonaqueous capillary electrophoresis (NACE) coupled with electrochemiluminescence (ECL) and electrochemistry (EC) dual detection. The mixture of acetonitrile (ACN) and 2-propanol containing 1M acetic acid (HAc), 20mM sodium acetate (NaAc), and 2.5mM tetrabutylammonium perchlorate (TBAP) was used as the electrophoretic buffer. Although a short capillary of 18cm was used, the decoupler was not needed and the separation efficiency was good. The linear ranges of atropine, anisodamine, and scopolamine were 0.5-50, 5-2000, and 50-2000microM, respectively. For six replicate measurements of 100microM scopolamine, 15microM atropine, and 200microM anisodamine, the RSDs of ECL intensity, EC current, and migration time were less than 3.6%, 4.5%, and 0.3%, respectively. In addition, because the organic buffer was used, the working electrode (Pt) was not easily fouled and did not need reactivation. The method was also applied for the determination of these three alkaloids in Flos daturae extract.

  6. ESP-102, a Combined Herbal Extract of Angelica gigas, Saururus chinensis, and Schisandra chinensis, Changes Synaptic Plasticity and Attenuates Scopolamine-Induced Memory Impairment in Rat Hippocampus Tissue

    PubMed Central

    Kim, Hyun-Bum; Hwang, Eun-Sang; Choi, Ga-Young; Lee, Seok; Park, Tae-Suk; Lee, Cheol-Won; Lee, Eun-Suk; Kim, Young-Choong; Kim, Sang Seong; Lee, Sung-Ok; Park, Ji-Ho

    2016-01-01

    ESP-102, an extract from Angelica gigas, Saururus chinensis, and Schisandra chinensis, has been used as herbal medicine and dietary supplement in Korea. Despite the numerous bioactivities in vitro and in vivo studies, its effects on neuronal networks remain elusive. To address the neuronal effect, we examined synaptic plasticity in organotypic hippocampal slice culture with multielectrode array. Our results showed an increase in excitatory postsynaptic potential (EPSP), indicating the induction of long-term potentiation (LTP), in the presence of ESP-102. In addition, the neuroprotective effect of ESP-102 was also tested by application of scopolamine to the hippocampal slice. Interestingly, ESP-102 competitively antagonized the preventative LTP effect induced by scopolamine. The scopolamine-induced reduction in brain-derived neurotrophic factor (BDNF) and GluR-2 expression was also rescued by ESP-102. In terms of mode of action, ESP-102 appears to act on the presynaptic region independent of AMPA/NMDA receptors. Based on these findings, ESP-102 can be suggested as a novel herbal ingredient with memory enhancing as well as neuroprotective effects. PMID:27298627

  7. Anti-Amnesic Effect of Fermented Ganoderma lucidum Water Extracts by Lactic Acid Bacteria on Scopolamine-Induced Memory Impairment in Rats

    PubMed Central

    Choi, Yu Jin; Yang, Hee Sun; Jo, Jun Hee; Lee, Sang Cheon; Park, Tae Young; Choi, Bong Suk; Seo, Kyoung Sun; Huh, Chang Ki

    2015-01-01

    This study investigated the anti-amnesic effect of fermented Ganoderma lucidum water extracts (GW) on scopolamine-induced memory impairment in rats. GW were fermented by the lactic acid bacterium Bifidobacterium bifidum (FGWB), followed by Lactobacillus sakei LI033 (FGWBL). To induce amnesia, scopolamine (1 mg/kg) was intraperitoneally injected into rats 30 min before the behavioral tests. Step-through latencies of rats treated with primary fermented extracts (300 mg/kg, FGWB) and secondary fermented extracts (300 mg/kg, FGWBL) were significantly longer than those of rats treated with GW (300 mg/kg) in the retention trial of the multiple trial passive avoidance test. In the Morris water maze task, FGWBL significantly shortened escape latencies in training trials. Furthermore, swimming times within the target zone during the probe trial with FGWBL were significantly higher than the GW and FGWB treatments. In addition, acetylcholinesterase activities were lower in the brains of scopolamine-treated rats treated with FGWBL. These results suggest that FGWBL could be useful to enhance learning memory and cognitive function via cholinergic dysfunction. PMID:26176000

  8. Protective Effects of Mangosteen Extract on H2O2-Induced Cytotoxicity in SK-N-SH Cells and Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Sattayasai, Jintana; Chaonapan, Pongsatorn; Arkaravichie, Tarinee; Soi-ampornkul, Rungtip; Junnu, Sarawut; Charoensilp, Patcharakajee; Samer, Jutima; Jantaravinid, Jiraporn; Masaratana, Patarabutr; Suktitipat, Bhoom; Manissorn, Juthatip; Thongboonkerd, Visith; Neungton, Neelobol; Moongkarndi, Primchanien

    2013-01-01

    Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against β-amyloid peptide (Aβ), induced cytotoxicity have been reported. Here, we further studied the protective effects of ME against oxidative stress induced by hydrogen peroxide (H2O2) and polychlorinated biphenyls (PCBs), and demonstrated the protection against memory impairment in mice. The cytoprotective effects of ME were measured as cell viability and the reduction in ROS activity. In SK-N-SH cell cultures, 200 μg/ml ME could partially antagonize the effects of 150 or 300 µM H2O2 on cell viability, ROS level and caspase-3 activity. At 200, 400 or 800 µg/ml, ME reduced AChE activity of SK-N-SH cells to about 60% of the control. In vivo study, Morris water maze and passive avoidance tests were used to assess the memory of the animals. ME, especially at 100 mg/kg body weight, could improve the animal’s memory and also antagonize the effect of scopolamine on memory. The increase in ROS level and caspase-3 activity in the brain of scopolamine-treated mice were antagonized by the ME treatment. The study demonstrated cytoprotective effects of ME against H2O2 and PCB-52 toxicity and having AChE inhibitory effect in cell culture. ME treatment in mice could attenuate scopolamine-induced memory deficit and oxidative stress in brain. PMID:24386444

  9. Allosteric interaction of the anticholinergic drug [N-(4-phenyl)-phenacyl-l-hyoscyamine] (Phenthonium) with nicotinic receptors of post-ganglionic sympathetic neurons of the rat vas deferens.

    PubMed

    Munhoz, Egberto; De Lima, Thereza C M; Souccar, Caden; Lapa, Antonio J; Lima-Landman, Maria Teresa R

    2009-08-15

    Phenthonium (Phen), a quaternary analog of hyoscyamine, is a blocker of muscarinic activity and an allosteric blocker of alpha(1)2betagammaepsilon nicotinic receptors. Specifically, Phenthonium increases the spontaneous release of acetylcholine at the motor endplate without depolarizing the muscle or inhibiting cholinesterase activity. This paper compares Phenthonium's effects on sympathetic transmission and on ganglionic nicotinic receptor activation. Neurotransmitter release and twitch of the rat vas deferens were induced either by electrical stimulation or by 1,1-dimethyl-4-phenylpiperazine (DMPP) activation of nicotinic receptors. Contractions independent of transmitter release were induced by noradrenaline and adenosine 5'-triphosphate (ATP). Phenthonium inhibited transmitter release and depressed twitch without changing the responsiveness to noradrenaline or ATP. Twitch depression did not occur after K(+)-channel blockade with 4-aminopyridine (4-AP) or charybdotoxin. DMPP had a similar effect, but high concentrations induced contraction of non-stimulated organs. Incubation of Phenthonium inhibited further DMPP twitch depression and non-competitively depressed the contractile responses elicited by DMPP. Furthermore, mecamylamine, but neither methyllycaconitine nor atropine, blocked the contraction elicited by DMPP. Phenthonium and DMPP are K(+)-channel openers that primarily inhibit sympathetic transmission. Contraction induced by DMPP was probably mediated by neuronal nicotinic receptor other than the alpha7 subtype. The blockade of DMPP contractile response was unrelated to Phenthonium's antimuscarinic or K(+)-channel opening activities. Since Phenthonium's quaternary chemical structure limits its membrane diffusion, the non-competitive inhibition of DMPP excitatory responses should be linked to allosteric interaction with neuronal nicotinic receptors that putatively qualify Phenthonium as a novel modulator of cholinergic synapses.

  10. Effects of drug countermeasures for space motion sickness on working memory in humans.

    PubMed

    Paule, Merle G; Chelonis, John J; Blake, Donna J; Dornhoffer, John L

    2004-01-01

    Space motion sickness (SMS) is a problem during the first 72 h of space flight and during transitions from different gravity environments. There currently are no effective drug countermeasures for SMS that also accommodate the retention of optimal cognitive function. This creates a dilemma for astronauts because cognitive skills are particularly important during gravity transitions (e.g., take-off and landing). To quantify the cognitive side effects of potential drug countermeasures, an automated delayed matching-to-sample (DMTS) procedure was used to assess visual working memory before and after drug countermeasures (meclizine 25 mg, scopolamine 0.4 mg, promethazine 25 mg, or lorazepam 1 mg, given orally approximately 45 min prior to testing) and/or the induction of SMS by vestibular stimulation in a rotary chair (spinning). Sixty-seven normal healthy volunteers (mean age, in years, 26.6+/-4.8 S.D.; 24 females and 43 males) each participated in two test sessions, one 'off' drug and one 'on' drug. Spinning by itself significantly decreased task accuracy (Acc) and choice response speed, especially at longer recall delays. Meclizine alone had no effect on Acc or speed with or without spinning. Scopolamine alone decreased Acc, and with spinning, slowed speed. Promethazine alone had no adverse effect, but combined with spinning, decreased Acc and speed. Lorazepam alone decreased speed, and with spinning, decreased Acc. The data suggest that, at clinically useful doses, the rank order of the drugs with the best cognitive profiles is meclizine>scopolamine>promethazine>lorazepam. PMID:15451046

  11. A Special Extract of Bacopa monnieri (CDRI-08) Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit GluN2B in the Brain of Scopolamine-Induced Amnesic Mice

    PubMed Central

    Rai, Rakesh; Singh, Hemant K.; Prasad, S.

    2015-01-01

    In the present communication, we have investigated effects of the CDRI-08, a well characterized extract of Bacopa monnieri, on expression of the GluN2B subunit of NMDAR in various brain regions of the scopolamine-induced amnesic mice. Our behavioral data reveal that scopolamine-treated amnesic mice exhibit significant decline in the spatial memory compared to the normal control mice. Our RT-PCR and immunoblotting data revealed that the scopolamine treatment resulted in a significant downregulation of the NMDAR GluN2B subunit expression in prefrontal cortex and hippocampus. Our enzyme assay data revealed that scopolamine caused a significant increase in the acetylcholinesterase activity in both the brain regions. Further, oral administration of the CDRI-08 to scopolamine-treated amnesic mice restored the spatial memory which was found to be associated with significant upregulation of the GluN2B subunit expression and decline in the acetylcholinesterase activity in prefrontal cortex as well as hippocampus towards their levels in the normal control mice. Our study provides the evidence for the mechanism underlying role of the Bacopa monnieri extract (CDRI-08) in restoring spatial memory in amnesic mice, which may have therapeutic implications. PMID:26413117

  12. Simultaneous determination of scopolamine, hyoscyamine and anisodamine in in vitro growth media of selected Solanaceae hairy roots by CE method.

    PubMed

    Dziomba, Szymon; Łepek, Teresa; Jaremicz, Zbigniew; Łuczkiewicz, Maria; Prahl, Adam; Kowalski, Piotr

    2015-09-15

    An electrophoretic method for fast separation of three tropane alkaloids (hyoscyamine, anisodamine and scopolamine) was presented. The substances were complete resolved in less than one minute due to utilization of relatively short capillary (20.2cm effective length) and high voltage (25kV). Detector probing frequency was found among the parameters that significantly affected the detection sensitivity. The performed experiments showed insufficient available probing frequency of used commercial spectrophotometric detector according to capillary electrophoresis (CE) separation potential. Under the optimized conditions the background electrolyte (BGE) was composed of 20mM Tris, 6mM HCl and 20mM NaCl (pH 8.50). All analyses were carried out in fused silica capillaries of 50μm (inner diameter) and 31.2cm (total capillary length). Samples were injected hydrodynamically (5s; 3.45kPa) without any sample preparation step and separation was performed at 25kV. The elaborated method was applied in plant cultures growth media analysis after incubation with hairy roots of selected Solanaceae species. The performed experiments proved the usefulness of CE in quality control of biotechnological processes. PMID:26253806

  13. Simultaneous determination of scopolamine, hyoscyamine and anisodamine in in vitro growth media of selected Solanaceae hairy roots by CE method.

    PubMed

    Dziomba, Szymon; Łepek, Teresa; Jaremicz, Zbigniew; Łuczkiewicz, Maria; Prahl, Adam; Kowalski, Piotr

    2015-09-15

    An electrophoretic method for fast separation of three tropane alkaloids (hyoscyamine, anisodamine and scopolamine) was presented. The substances were complete resolved in less than one minute due to utilization of relatively short capillary (20.2cm effective length) and high voltage (25kV). Detector probing frequency was found among the parameters that significantly affected the detection sensitivity. The performed experiments showed insufficient available probing frequency of used commercial spectrophotometric detector according to capillary electrophoresis (CE) separation potential. Under the optimized conditions the background electrolyte (BGE) was composed of 20mM Tris, 6mM HCl and 20mM NaCl (pH 8.50). All analyses were carried out in fused silica capillaries of 50μm (inner diameter) and 31.2cm (total capillary length). Samples were injected hydrodynamically (5s; 3.45kPa) without any sample preparation step and separation was performed at 25kV. The elaborated method was applied in plant cultures growth media analysis after incubation with hairy roots of selected Solanaceae species. The performed experiments proved the usefulness of CE in quality control of biotechnological processes.

  14. Evaluation of acetylcholine, seizure activity and neuropathology following high-dose nerve agent exposure and delayed neuroprotective treatment drugs in freely moving rats.

    PubMed

    Acon-Chen, Cindy; Koenig, Jeffrey A; Smith, Garrett R; Truitt, Amber R; Thomas, Thaddeus P; Shih, Tsung-Ming

    2016-06-01

    Organophosphorus nerve agents such as soman (GD) inhibit acetylcholinesterase, producing an excess of acetylcholine (ACh), which results in respiratory distress, convulsions and status epilepticus that leads to neuropathology. Several drugs (topiramate, clobazam, pregnanolone, allopregnanolone, UBP 302, cyclopentyladenosine [CPA], ketamine, midazolam and scopolamine) have been identified as potential neuroprotectants that may terminate seizures and reduce brain damage. To systematically evaluate their efficacy, this study employed in vivo striatal microdialysis and liquid chromatography to respectively collect and analyze extracellular ACh in freely moving rats treated with these drugs 20 min after seizure onset induced by a high dose of GD. Along with microdialysis, EEG activity was recorded and neuropathology assessed at 24 h. GD induced a marked increase of ACh, which peaked at 30 min post-exposure to 800% of control levels and then steadily decreased toward baseline levels. Approximately 40 min after treatment, only midazolam (10 mg/kg) and CPA (60 mg/kg) caused a significant reduction of ACh levels, with CPA reducing ACh levels more rapidly than midazolam. Both drugs facilitated a return to baseline levels at least 55 min after treatment. At 24 h, only animals treated with CPA (67%), midazolam (18%) and scopolamine (27%) exhibited seizure termination. While all treatments except for topiramate reduced neuropathology, CPA, midazolam and scopolamine showed the greatest reduction in pathology. Our results suggest that delayed treatment with CPA, midazolam, or scopolamine is effective at reducing GD-induced seizure activity and neuropathology, with CPA and midazolam capable of facilitating a reduction in GD-induced ACh elevation. PMID:27329284

  15. Analytical developments in toxicological investigation of drug-facilitated sexual assault.

    PubMed

    Negrusz, Adam; Gaensslen, R E

    2003-08-01

    This paper gives a general overview of the drug-facilitated sexual assault phenomenon. Sexual assault perpetrated on both women and men, while incapacitated by so-called date-rape drugs, recently became the focus of many investigations conducted by law enforcement agencies in the US throughout the 1990s; an alarming increase in reports of this crime as well as in the number of scientific publications on drug-facilitated sexual assault has been observed. The list of drugs reportedly associated with sexual assault is long and among others includes flunitrazepam with other benzodiazepines such as diazepam, temazepam, clonazepam, oxazepam, as well as gamma-hydroxybutyrate (GHB), ketamine, and scopolamine. We discuss the most recent analytical developments in the toxicological investigation of drug-facilitated rape designed to reveal drug presence and that may help successfully prosecute perpetrators. PMID:12682705

  16. PWZ-029, an inverse agonist selective for α₅ GABAA receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats.

    PubMed

    Milić, Marija; Timić, Tamara; Joksimović, Srđan; Biawat, Poonam; Rallapalli, Sundari; Divljaković, Jovana; Radulović, Tamara; Cook, James M; Savić, Miroslav M

    2013-03-15

    Inverse agonism at the benzodiazepine site of α(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for α(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an α(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2, 5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5, 10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective α(5) GABA(A) inverse agonists.

  17. The effects of tamoxifen on spatial and nonspatial learning and memory impairments induced by scopolamine and the brain tissues oxidative damage in ovariectomized rats

    PubMed Central

    Karimi, Sareh; Hejazian, Seyed Hassan; Alikhani, Vajiheh; Hosseini, Mahmoud

    2015-01-01

    Background: Modulatory effects of tamoxifen (TAM) on the central nervous system have been reported. The effects of TAM on spatial and nonspatial learning and memory impairments induced by scopolamine and the brain tissues oxidative damage was investigated. Materials and Methods: The ovariectomized (OVX) rats were divided and treated: (1) Control (saline), (2) scopolamine (Sco; 2 mg/kg, 30 min before behavioral tests), (3–5) Sco-TAM 1, Sco-TAM 3 and Sco-TAM 10. TAM (1, 3 or 10 mg/kg; i.p.) was daily administered for 6 weeks. Results: In Morris water maze (MWM), both the latency and traveled distance in the Sco-group were higher than control (P < 0.001) while, in the Sco-TAM 10 group it was lower than Sco-group (P < 0.05). In passive avoidance test, the latency to enter the dark compartment was higher than control (P < 0.05 – P < 0.01). Pretreatment by all three doses of TAM prolonged the latency to enter the dark compartment compared to Sco-group (P < 0.05 – P < 0.001). The brain tissues malondialdehyde (MDA) concentration was increased while, superoxide dismutase activity (SOD) decreased in the Sco-group compared to control (P < 0.05 – P < 0.01). Pretreatment by TAM lowered the concentration of MDA while, increased SOD compared to Sco-group (P < 0.05 – P < 0.001). Conclusions: It is suggested that TAM prevents spatial and nonspatial learning and memory impairments induced by scopolamine in OVX rats. The possible mechanism(s) might at least in part be due to protection against the brain tissues oxidative damage. PMID:26601084

  18. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    PubMed

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice.

  19. Decreasing the load? Is a Multidisciplinary Multistep Medication Review in older people an effective intervention to reduce a patient's Drug Burden Index? Protocol of a randomised controlled trial

    PubMed Central

    van der Meer, Helene G; Wouters, Hans; van Hulten, Rolf; Pras, Niesko; Taxis, Katja

    2015-01-01

    Introduction Older people often use medications with anticholinergic or sedative side effects which increase the risk of falling and worsen cognitive impairment. The Drug Burden Index (DBI) is a measure of the burden of anticholinergic and sedative medications. Medication reviews are typically done by a pharmacist in collaboration with a general practitioner to optimise the medication use and reduce these adverse drug events. We will evaluate whether a Multidisciplinary Multistep Medication Review (3MR) is an effective intervention to reduce a patient's DBI. Methods A randomised controlled trial including 160 patients from 15 community pharmacies will be conducted. Per pharmacy, 1 pharmacist will perform a structured 3MR in close collaboration with the general practitioner, including the objective to reduce the DBI. Analysis Primary outcome—the difference in proportion of patients having a decrease in DBI≥0.5 in the intervention and control groups at follow-up. Secondary outcomes—anticholinergic and sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission, and mortality. Ethics and dissemination The burden of patients will be kept at a minimum. The 3MR can be considered as usual care by the pharmacist and general practitioner. Medical specialists will be consulted, if necessary. The intervention is specifically aimed at older community-dwelling patients in an attempt to optimise prescribing, in particular, to reduce medication with anticholinergic and sedative properties. Study results will be published in peer-reviewed journals and will be distributed through information channels targeting professionals. Trial registration number NCT02317666; Pre-results. PMID:26700279

  20. Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations.

    PubMed

    Safar, Marwa M; Arab, Hany H; Rizk, Sherine M; El-Maraghy, Shohda A

    2016-04-01

    Vascular endothelial dysfunction plays a key role in the pathogenesis of Alzheimer's disease (AD). Patients with AD have displayed decreased circulating endothelial progenitor cells (EPCs) which repair and maintain the endothelial function. Transplantation of EPCs has emerged as a promising approach for the management of cerebrovascular diseases including ischemic stroke, however, its impact on AD has been poorly described. Thus, the current study aimed at investigating the effects of bone marrow-derived (BM) EPCs transplantation in repeated scopolamine-induced cognitive impairment, an experimental model that replicates biomarkers of AD. Intravenously transplanted BM-EPCs migrated into the brain of rats and improved the learning and memory deficits. Meanwhile, they mitigated the deposition of amyloid plaques and associated histopathological alterations. At the molecular levels, BM-EPCs blunted the increase of hippocampal amyloid beta protein (Aβ), amyloid precursor protein (APP) and reinstated the Aβ-degrading neprilysin together with downregulation of p-tau and its upstream glycogen synthase kinase-3β (GSK-3β). They also corrected the perturbations of neurotransmitter levels including restoration of acetylcholine and associated esterase along with dopamine, GABA, and the neuroexitatory glutamate. Furthermore, BM-EPCs induced behavioral recovery via boosting of vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and its upstream cAMP response element binding (CREB), suppression of the proinflammatory tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and upregulation of interleukin-10 (IL-10). BM-EPCs also augmented Nrf2 and seladin-1. Generally, these actions were analogous to those exerted by adipose tissue-derived mesenchymal stem cells (AT-MSCs) and the reference anti-Alzheimer donepezil. For the first time, these findings highlight the beneficial actions of BM-EPCs against the memory

  1. D-cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus.

    PubMed

    Portero-Tresserra, Marta; Del Olmo, Nuria; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma; Vale-Martínez, Anna

    2014-11-01

    Previous research has demonstrated that systemic D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate receptor (NMDAR), enhances memory processes in different learning paradigms and attenuates mnemonic deficits produced by diverse pharmacological manipulations. In the present study two experiments were conducted in rats to investigate whether DCS administered in the hippocampus may rescue relational memory deficits and improve deficient synaptic plasticity, both induced by an intracerebral injection of the muscarinic receptor antagonist scopolamine (SCOP). In experiment 1, we assessed whether DCS would prevent SCOP-induced amnesia in an olfactory learning paradigm requiring the integrity of the cholinergic system, the social transmission of food preference (STFP). The results showed that DCS (10 μg/site) injected into the ventral hippocampus (vHPC) before STFP acquisition compensated the 24-h retention deficit elicited by post-training intra-vHPC SCOP (40 μg/site), although it did not affect memory expression in non-SCOP treated rats. In experiment 2, we evaluated whether the perfusion of DCS in hippocampal slices may potentiate synaptic plasticity in CA1 synapses and thus recover SCOP-induced deficits in long-term potentiation (LTP). We found that DCS (50 µM and 100 µM) was able to rescue SCOP (100 µM)-induced LTP maintenance impairment, in agreement with the behavioral findings. Additionally, DCS alone (50 µM and 100 µM) enhanced field excitatory postsynaptic potentials prior to high frequency stimulation, although it did not significantly potentiate LTP. Our results suggest that positive modulation of the NMDAR, by activation of the glycine-binding site, may compensate relational memory impairments due to hippocampal muscarinic neurotransmission dysfunction possibly through enhancements in LTP maintenance.

  2. A review of options for treating sialorrhea in amyotrophic lateral sclerosis.

    PubMed

    Banfi, Paolo; Ticozzi, Nicola; Lax, Agata; Guidugli, Giulia Andrea; Nicolini, Antonello; Silani, Vincenzo

    2015-03-01

    Sialorrhea or drooling represents quite a common problem in patients with amyotrophic lateral sclerosis (ALS). In this review, we describe the possible treatments for this issue. Current medical management is not always effective: anticholinergic drugs (atropine, glycopyrrolate, amitriptyline, hyoscyamine, and transdermal scopolamine) are often used, but there is very little evidence of their effectiveness in patients with ALS. More invasive treatments, such as botulinum toxin injections and/or radiation therapy in the salivary glands, can be considered when anticholinergic drugs are not effective. In this review, we also explore the possible surgical options for treatment of sialorrhea. Although no specific studies have been conducted on patients with ALS, surgical therapies might represent a valid option for treatment of sialorrhea since there is no tachyphylaxis or need for repeated therapeutic sessions.

  3. Effect of some smooth muscle relaxant drugs on calcium-related phenomena.

    PubMed

    Ronca-Testoni, S; Hrelia, S; Hakim, G; Ronca, G; Rossi, C A

    1984-04-30

    Some smooth muscle relaxant drugs devoid of anticholinergic action have been tested for their interaction with calmodulin, calmodulin-stimulated cyclic nucleotide phosphodiesterase activity, and uterine membrane binding sites for nitrendipine and adenosine. The myolytic activity of octylonium bromide and pinaverium bromide may be due to their interaction with calmodulin-dependent systems. Trimebutine maleate does not bind either to calmodulin or to nitrendipine and adenosine receptors. Tiropramide has no effect on calmodulin-dependent systems and on Ca2+ channels but it shows a competition for the A2-type adenosine receptors. PMID:6329247

  4. Simultaneous analysis of hyoscyamine, scopolamine, 6beta-hydroxyhyoscyamine and apoatropine in Solanaceous hairy roots by reversed-phase high-performance liquid chromatography.

    PubMed

    Kursinszki, László; Hank, Hajnalka; László, Imre; Szoke, Eva

    2005-10-14

    A new high-performance liquid chromatographic method is described for tropane alkaloid analysis in genetically transformed root cultures of Datura innoxia Mill. and Atropa belladonna L. Sample preparation, tropane alkaloid extraction with chloroform-methanol-concentrated ammonia 15:5:1 (v/v/v), was followed by solid-phase extraction on Supelclean LC-18 cartridges. Optimized conditions and careful pH control resulted in high recovery and reproducibility. Simultaneous determination of apoatropine, 6beta-hydroxyhyoscyamine, hyoscyamine and scopolamine was performed by HPLC on C18 (2) reversed-phase column. The application of Luna new-generation silica-based stationary phase resulted in excellent peak shapes using an ion-pair reagent and triethanolamine free mobile phase and allowed to exploit the full power of pH-dependent selectivity. Simplicity and improved selectivity make this method a preferred alternative of published ion-pair chromatographic methods. Validation studies proved that the global method has good repeatability and satisfactory recovery. Absolute limits of detection were 0.6, 0.6, and 0.8 ng for hyoscyamine, 6beta-hydroxyhyoscyamine, and scopolamine respectively.

  5. Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study

    PubMed Central

    Ozarowski, Marcin; Thiem, Barbara; Mikolajczak, Przemyslaw L.; Piasecka, Anna; Kachlicki, Piotr; Szulc, Michal; Kaminska, Ewa; Bogacz, Anna; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Budzianowski, Jaromir; Kędziora, Izabela; Seremak-Mrozikiewicz, Agnieszka; Czerny, Boguslaw; Bobkiewicz-Kozłowska, Teresa

    2015-01-01

    Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots. PMID:26483842

  6. Bacopa monniera (CDRI-08) Upregulates the Expression of Neuronal and Glial Plasticity Markers in the Brain of Scopolamine Induced Amnesic Mice

    PubMed Central

    Konar, Arpita; Gautam, Akash; Thakur, M. K.

    2015-01-01

    Preclinical studies on animal models have discerned the antiamnesic and memory-enhancing potential of Bacopa monniera (Brahmi) crude extract and standardized extracts. These studies primarily focus on behavioral consequences. However, lack of information on molecular underpinnings has limited the clinical trials of the potent herb in human subjects. In recent years, researchers highlight plasticity markers as molecular correlates of amnesia and being crucial to design therapeutic targets. In the present report, we have investigated the effect of a special extract of B. monniera (CDRI-08) on the expression of key neuronal (BDNF and Arc) and glial (GFAP) plasticity markers in the cerebrum of scopolamine induced amnesic mice. Pre- and postadministration of CDRI-08 ameliorated amnesic effect of scopolamine by decreasing acetyl cholinesterase activity and drastically upregulating the mRNA and protein expression of BDNF, Arc, and GFAP in mouse cerebrum. Interestingly, the plant extract per se elevated BDNF and Arc expression as compared to control but GFAP was unaltered. In conclusion, our findings provide the first molecular evidence for antiamnesic potential of CDRI-08 via enhancement of both neuronal and glial plasticity markers. Further investigations on detailed molecular pathways would encourage therapeutic application of the extract in memory disorders. PMID:26413129

  7. The coumarin scopoletin potentiates acetylcholine release from synaptosomes, amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and age-impaired memory

    PubMed Central

    Hornick, A.; Lieb, A.; Vo, N.P.; Rollinger, J.M.; Stuppner, H.; Prast, H.

    2011-01-01

    In a previous study the simple, naturally derived coumarin scopoletin (SCT) was identified as an inhibitor of acetylcholinesterase (AChE), using a pharmacophore-based virtual screening approach. In this study the potential of SCT as procholinergic and cognition-enhancing therapeutic was investigated in a more detailed way, using different experimental approaches like measuring newly synthesized acetylcholine (ACh) in synaptosomes, long-term potentiation (LTP) experiments in hippocampal slices, and behavior studies. SCT enhanced the K+-stimulated release of ACh from rat frontal cortex synaptosomes, showing a bell-shaped dose effect curve (Emax: 4 μM). This effect was blocked by the nicotinic ACh receptor (nAChR) antagonists mecamylamine (MEC) and dihydro-β-erythroidine (DHE). The nAChR agonist (and AChE inhibitor) galantamine induced a similar increase in ACh release (Emax: 1 μM). SCT potentiated LTP in hippocampal slices of rat brain. The high-frequency stimulation (HFS)-induced, N-methyl-D-aspartate (NMDA) receptor dependent LTP of field excitatory postsynaptic potentials at CA3-CA1 synapses was greatly enhanced by pre-HFS application of SCT (4 μM for 4 min). This effect was mimicked by nicotine (2 μM) and abolished by MEC, suggesting an effect on nAChRs. SCT did not restore the total inhibition of LTP by NMDA receptor antagonist d, l-2-amino-5-phosphonopentanoic acid (AP-5). SCT (2 μg, i.c.v.) increased T-maze alternation and ameliorated novel object recognition of mice with scopolamine-induced cholinergic deficit. It also reduced age-associated deficits in object memory of 15–18-month-old mice (2 mg/kg sc). Our findings suggest that SCT possesses memory-improving properties, which are based on its direct nAChR agonistic activity. Therefore, SCT might be able to rescue impaired cholinergic functions by enhancing nAChR-mediated release of neurotransmitters and promoting neural plasticity in hippocampus. PMID:21945033

  8. Evaluation of a purification procedure for the muscarinic receptor for the purpose of quantitative receptor assays of anticholinergics. Part B: The solubilized receptor.

    PubMed

    Smisterová, J; Ensing, K; de Boer, J; de Zeeuw, R A

    1995-11-01

    For the purpose of quantitative receptor assays, a three-step solubilization procedure including three optimization sets for muscarinic receptor from calf striatum was developed. The first step includes the extraction of the P2-pellet with n-hexane and consequently with 2 M NaCl. By the latter, 39% of non-receptor proteins was extracted. The resulting pellet (NaCl-pellet), enriched in muscarinic receptors by a factor of 1.5-1.7, was solubilized with 1% digitonin. The binding parameters of the solubilized receptor were determined for the tertiary 3H-dexetimide (3H-DEX) and the quaternary 3H-N-methylscopolamine (3H-NMS). The resulting receptor density measured with 3H-dexetimide was lower (43.3% of that for the NaCl-pellet) than that for 3H-N-methyl-scopolamine (56.7%). The treatment with digitonin preserved the high affinity for 3H-N-methylscopolamine (Kd = 0.645 nM), however the affinity of 3H-dexetimide decreased after solubilization (Kd = 8.526 nM). The use of solubilized receptors in combination with hydrophilic 3H-NMS allows to increase the ratio specific/non-specific binding, since the non-specific binding for this ligand to the solubilized preparation is lower when compared with membrane-bound receptors. The above solubilization procedure was found preferable over directly solubilizing the P2-pellet since (a) the receptor density for 3H-NMS was higher for the solubilized NaCl-pellet by a factor of about 1.7, and (b) the treatment of the P2-pellet with digitonin resulted in a lowering of the Kd to 2.422 nM. However, with respect to the plasma effect on the ligand binding, both solubilized preparations give similar results. The use of the solubilized NaCl-pellet or the P2-pellet can considerably improve the quantitative receptor assays of plasma samples. Unlike the membrane-bound receptor, a high volume of plasma, such as 400 microliters, can be added to the assay without any influence on the 3H-DEX binding when solubilized preparation is used. PMID:8570570

  9. Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential.

    PubMed

    Ahnaou, A; Huysmans, H; Jacobs, T; Drinkenburg, W H I M

    2014-11-01

    Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations. Cognition enhancers elicited systematic ("fingerprint") enhancement of cortical slow theta (4.5-6 Hz) and gamma (30.5-50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to

  10. Atropa Belladonna intoxication: a case report

    PubMed Central

    Berdai, Mohamed Adnane; Labib, Smael; Chetouani, Khadija; Harandou, Mustapha

    2012-01-01

    Atropa Belladonna is a poisonous plant also called deadly nightshade. Its roots, leaves and fruits contain alkaloids: atropine, hyocyamine and scopolamine. The risk of poisoning in children is important because of possible confusion with other berries. Atropa Belladonna acute intoxication is a severe condition, it's should be considered in the presence of anti-cholinergic toxidrome, the differential diagnosis include other plants or psychoactive drugs containing atropine. The treatment is mainly symptomatic including gastrointestinal decontamination with activated charcoal. In severe cases, physostigmine can be used as an antidote. We report the case of 11 year old girl with Atropa Belladonna poisoning which was administrated in a therapeutic purpose as a remedy to jaundice. The child presented essentially a central anti-cholinergic syndrome. She was admitted in the intensive care unit, the progression was favorable with symptomatic treatment. PMID:22655106

  11. Lactobacillus casei-01 facilitates the ameliorative effects of proanthocyanidins extracted from lotus seedpod on learning and memory impairment in scopolamine-induced amnesia mice.

    PubMed

    Xiao, Juan; Li, Shuyi; Sui, Yong; Wu, Qian; Li, Xiaopeng; Xie, Bijun; Zhang, Mingwei; Sun, Zhida

    2014-01-01

    Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (10(9) cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice.

  12. Lactobacillus casei-01 facilitates the ameliorative effects of proanthocyanidins extracted from lotus seedpod on learning and memory impairment in scopolamine-induced amnesia mice.

    PubMed

    Xiao, Juan; Li, Shuyi; Sui, Yong; Wu, Qian; Li, Xiaopeng; Xie, Bijun; Zhang, Mingwei; Sun, Zhida

    2014-01-01

    Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (10(9) cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice. PMID:25396737

  13. Drug utilization and prescribing patterns in a skilled nursing facility: the need for a rational approach to therapeutics.

    PubMed

    Segal, J L; Thompson, J F; Floyd, R A

    1979-03-01

    A study was made of 50 patients drawn at random from a Skilled Nursing Facility (SNF) attended by seven physicians. For 59 percent of these patients, polypharmacy was practiced but no substantiating diagnoses were recorded. Approximately half of the drugs were administered pro re nata. More drugs were prescribed in potentially toxic dosages than in subtherapeutic dosages. The risk of an adverse drug reaction (ADR) was most often associated with anticholinergic agents, sedative-hypnotic drugs, and neuroleptics (thioridazine and chlorpromazine), particularly when prescribed concurrently. Risk of an ADR was highest when a drug was prescribed without recording a definite diagnostic indication. Lack of consistency by individual physicians in their approaches to the therapy of similar disease entities in comparable patients tended to support the concept of peer review in SNFs and also the need for teaching a rational approach to therapeutics in SNFs based on clinical pharmacology as applied to the elderly. PMID:429730

  14. Inhaled drugs as risk factors for community-acquired pneumonia.

    PubMed

    Almirall, J; Bolíbar, I; Serra-Prat, M; Palomera, E; Roig, J; Hospital, I; Carandell, E; Agustí, M; Ayuso, P; Estela, A; Torres, A

    2010-11-01

    The effect of inhaled drugs in community-acquired pneumonia (CAP) is unclear. This case-control study was designed to determine whether inhaled drugs were risk factors for CAP. All incident cases of confirmed CAP that occurred over 1 yr in patients with chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD) or asthma were included, as well as CB, COPD and asthma controls. Risk factors for CAP and inhaled treatment were recorded during a personal interview. An effect of inhaled drugs on the risk of CAP was observed in COPD and asthma patients after adjusting for the effect of other respiratory diseases and their concomitant treatments. In COPD patients, inhaled steroids had a risk OR of 3.26 (95% CI 1.07-9.98) and in asthma patients inhaled anticholinergics had a risk OR of 8.80 (95% CI 1.02-75.7). In CB patients, no association with CAP was observed for any inhaler. These effects were independent of adjusting variables related to severity and other respiratory and non-respiratory risk factors for CAP, including vaccines. Inhaled β(2)-adrenergic agonists did not show a significant effect on the risk of CAP in any of the respiratory diseases. Inhaled steroids may favour CAP in COPD patients, whereas anticholinergics may favour CAP in asthma patients. It is difficult to differentiate the effect of inhaled therapy from the effect of COPD or asthma severity on the risk of CAP, and these relationships may not be causal, but could call attention to inhaled therapy in COPD and asthma patients.

  15. Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice.

    PubMed

    He, Dandan; Wu, Hui; Wei, Yue; Liu, Wei; Huang, Fei; Shi, Hailian; Zhang, Beibei; Wu, Xiaojun; Wang, Changhong

    2015-12-01

    Harmine, a β-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency.

  16. Scopolamine Transdermal Patch

    MedlinePlus

    ... patch from its protective pouch. To expose the adhesive surface of the patch, the clear plastic protective ... peeled off and discarded. Contact with the exposed adhesive layer should be avoided to prevent contamination of ...

  17. Arousal and stability - The effects of five new sympathomimetic drugs suggest a new principle for the prevention of space motion sickness

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Calkins, D. S.; Mandell, A. J.

    1986-01-01

    Sympathomimetic agents are frequent components in antimotion-sickness drug combinations because of their usefulness in counteracting the sedation caused by stressful motion or resulting from the administration of other antimotion-sickness drugs. The noradrenergic neurochemistry of the brain's arousal-attentional systems prompted us to evaluate the efficacy of five new sympathomimetic drugs and to further define the role of arousal in susceptibility to motion. Subjects were orally administered methamphetamine (20 mg), phenmetrazine (25 mg), phentermine (37.5 mg), methylphenidate (20 mg), or pemoline (75 mg) 2 h prior to taking a Staircase Profile Test. All of the drugs increased resistance to stressful coriolis stimulation by 80-120 percent. Methylphenidate and pemoline showed fewer side effects. These findings, interpreted in conjunction with the documented inefficacy of most anticholinergic and antihistaminergic drugs tested to date, suggest that sympathomimetic drugs or a generalized state of arosusal can inhibit the development of motion sickness.

  18. Chromium-induced tropane alkaloid production and H6H gene expression in Atropa belladonna L. (Solanaceae) in vitro-propagated plantlets.

    PubMed

    Vakili, Bahareh; Karimi, Farah; Sharifi, Mozafar; Behmanesh, Mehrdad

    2012-03-01

    Hyoscyamine and scopolamine tropane alkaloids found in several solanaceous plants are anticholinergic drugs. Hyoscyamine 6β-hydroxylase (H6H) catalyzes two consecutive oxidation reactions. The first reaction is the hydroxylation of hyoscyamine to 6β-hydroxyhyoscyamine and the second is epoxidation of 6β-hydroxyhyoscyamine yielding scopolamine that is the final metabolite in the tropane alkaloid biosynthetic pathway. The effects of trivalent chromium as KCr (SO4)(2) on the production of tropane alkaloids and the expression of hyoscyamine 6β-hydroxylase gene (h6h) were studied in micro-propagated Atropa belladonna L. plantlets. The results showed that chromium treatment decreased the growth parameters (weights and lengths of the plantlets) and chlorophyll contents and increased proline contents. Moreover, semiquantitave RT-PCR analysis showed that the transcript level of H6H increased under chromium treatment. This treatment also increased hyoscyamine and scopolamine contents as shown by HPLC analysis. Changes of scopolamine contents correlate with the expression levels of h6h gene under different concentrations of chromium. PMID:22305072

  19. The effects of moclobemide on cognition.

    PubMed

    Wesnes, K A; Simpson, P M; Christmas, L; Anand, R; McClelland, G R

    1989-01-01

    The mental ability of the elderly is frequently compromised by age-associated cognitive declines, which may be result of cholinergic deterioration. Depression is accompanied by cognitive performance impairments, and recent work suggests these may be more severe in the elderly. Antidepressants with anticholinergic side-effects, such as the tricyclics, should thus be used with caution in the elderly. A potential advantage of new antidepressants which are relatively free of anticholinergic effects, may be in a reduced liability to impair cognition, whilst maintaining at least equal antidepressant potency. The effects of moclobemide, a novel reversible monoamine oxidase inhibitor, have been studied in both young and elderly volunteers using computerized assessment of a variety of aspects of cognition. In the young the drug was studied within a scopolamine model of the cognitive effects of aging and dementia, while, in the elderly, the cognitive effects of the drug were compared to those of trazodone. In the scopolamine model, moclobemide was significantly superior to placebo and other compounds in antagonizing the cognitive impairments resulting from cholinergic blockade. In the elderly, some improvements were found with moclobemide, particularly in memory, and while an impairment to vigilance was observed, this effect was considerably less marked than with trazodone. Moclobemide would thus appear to have an advantage over antidepressant compounds such as the tricyclics of having a lower liability to impair cognitive efficiency. However, to establish this in depressed patients it will be necessary to incorporate sensitive assessments of cognitive efficiency into trials of the drug in young and elderly populations.

  20. Evaluation of antimotion sickness drug side effects on performance

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

    The effects of antimotion-sickness drugs on the performance in computerized-pursuit-meter tests of groups of ten 18-30-yr-old male and female subjects are investigated experimentally using double-blind placebo techniques. The results are presented in tables and graphs and discussed in detail. The proficiency scores are as good as or better than placebo values for subjects given d-amphetamine (DA) 5 or 10 mg, promethazine (P) 25 mg + scopolamine (S) 400 ng + DA 10 mg, S 1 mg + DA 10 mg, S 250-600 ng, marezine 50 mg, meclizine 50 mg, dimenhydrinate 50 mg, S 1 mg + DA 5 mg, or P 25 mg + DA 10 mg. Significantly lower scores are seen in subjects given S 800 ng or 1 mg, P 25 mg (oral or IM), P 25 mg + S 400 ng, and P 25 mg oral + P 25 mg IM + DA 10 mg.

  1. Simultaneous determination of atropine, scopolamine, and anisodamine from Hyoscyamus niger L. in rat plasma by high-performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetics study.

    PubMed

    Zhang, Peiting; Li, Yemeng; Liu, Guanghui; Sun, Xiuman; Zhou, Yuting; Deng, Xuejiao; Liao, Qiongfeng; Xie, Zhiyong

    2014-10-01

    In order to investigate the pharmacokinetics of tropane alkaloids in Hyoscyamus niger L., a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of atropine, scopolamine, and anisodamine in rat plasma is developed and fully validated, using homatropine as an internal standard. The separation of the four compounds was carried out on a BDS Hypersil C18 column using a mobile phase consisting of acetonitrile and water (containing 10 mmol ammonium acetate). Calibration curves were linear from 0.2 to 40 ng/mL for atropine, scopolamine, and from 0.08 to 20 ng/mL for anisodamine. The precision of three analytes was <5.89% and the accuracy was between -1.04 to 2.94%. This method is successfully applied to rat pharmacokinetics analysis of the three tropane alkaloids after oral administration of H. niger extract. The maximum concentration of these three tropane alkaloids was reached within 15 min, and the maximum concentrations were 31.36 ± 7.35 ng/mL for atropine, 49.94 ± 2.67 ng/mL for scopolamine, and 2.83 ± 1.49 ng/mL for anisodamine. The pharmacokinetic parameters revealed areas under the curve of 22.76 ± 5.80, 16.80 ± 3.08, and 4.31 ± 1.21 ng/h mL and mean residence times of 2.08 ± 0.55, 1.19 ± 0.45, and 3.28 ± 0.78 h for atropine, scopolamine, and anisodamine, respectively.

  2. Efficient biosynthesis of rare natural product scopolamine using E. coli cells expressing a S14P/K97A mutant of hyoscyamine 6β-hydroxylase AaH6H.

    PubMed

    Cao, Yue-De; He, Yu-Cai; Li, Hao; Kai, Guo-Yin; Xu, Jian-He; Yu, Hui-Lei

    2015-10-10

    Hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), an α-ketoglutarate dependent dioxygenase catalyzes the hydroxylation of (-)-hyoscyamine and the subsequent epoxidation of 6β-hydroxyhyoscyamine to form scopolamine, a valuable natural alkaloid. In this study, random mutagenesis and site-directed saturation mutagenesis were used to enhance the hydroxylation activity of H6H from Anisodus acutangulus (AaH6H). A double mutant, AaH6HM1 (S14P/K97A), showed a 3.4-fold improved hydroxylation activity compared with the wild-type enzyme, and the in vivo epoxidation activity was also improved by 2.3 times. After 34h cultivation of Escherichia coli cells harboring Aah6hm1 in a 5-L bioreactor with a working volume of 3L, scopolamine was produced via a single-enzyme-mediated two-step transformation from 500mgL(-1) (-)-hyoscyamine in 97% conversion, and 1.068g of the product were isolated, corresponding to a space-time yield of 251mgL(-1)d(-1). This study shows that the protein engineering of some key enzymes is a promising and effective way for improving the production of rare natural products such as scopolamine.

  3. Determination of the effectiveness of components of the herbal medicine Toki-Shakuyaku-San and fractions of Angelica acutiloba in improving the scopolamine-induced impairment of rat's spatial cognition in eight-armed radial maze test.

    PubMed

    Hatip-Al-Khatib, Izzettin; Egashira, Nobuaki; Mishima, Kenichi; Iwasaki, Katsunori; Iwasaki, Kiyo; Kurauchi, Kouji; Inui, Keiichiro; Ikeda, Tomoaki; Fujiwara, Michihiro

    2004-09-01

    The improving effects of various components of Toki-Shakuyaku-San (TSS) and fractions isolated from Angelica acutiloba Radix (Toki) on scopolamine-induced spatial memory impairment were investigated in eight-armed radial maze. The scopolamine-induced memory impairment was characterized by prominent increase of error choices in addition to decreased correct choices. Toki, Cnidium officinale Rhizoma (Senkyu), Poria cocos Hoelen (Bukuryo), Alisma orientale Rhizoma (Takusha), and Atractylodes lancea Rhizoma (Sojutsu) increased the correct choices, while only the Toki, Sojutsu, and Takusha decreased the error choices. No effect was produced by Paeonia lactiflora Radix (Shakuyaku). Investigation of effects of fractions isolated from Toki revealed that its activity mainly resided in the butanol layer and its contents of N-methyl-beta-carboline-3-carboxamide and amines. Moreover, the alkaloid, internal and external solutions (containing poly-, di-, and monosaccharides) obtained by dialysis with Visking cellophane tubing also improved the memory. However, no improving properties were detected for methanol and hexanol layers, L-(-)-tryptophan, L-arginine, L-(-)-lysine, and choline chloride. The results showed that the TSS components could improve the reference and working memory impaired by scopolamine. The improving effect of TSS is produced greatly by the Toki component, the activity of which was greatly produced by the fraction extracted by butanol. PMID:15351791

  4. Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), More Than Meets the Eye: A Critical Review

    PubMed Central

    Qandil, Amjad M.

    2012-01-01

    The design and the synthesis of prodrugs for nonsteroidal anti-inflammatory drugs (NSAIDs) have been given much attention by medicinal chemists, especially in the last decade. As a therapeutic group, NSAIDs are among the most widely used prescribed and over the counter (OTC) medications. The rich literature about potential NSAID prodrugs clearly shows a shift from alkyl, aryalkyl or aryl esters with the sole role of masking the carboxylic acid group, to more elaborate conjugates that contain carefully chosen groups to serve specific purposes, such as enhancement of water solubility and dissolution, nitric oxide release, hydrogen sulfide release, antioxidant activity, anticholinergic and acetylcholinesterase inhibitory (AChEI) activity and site-specific targeting and delivery. This review will focus on NSAID prodrugs that have been designed or were, later, found to possess intrinsic pharmacological activity as an intact chemical entity. Such intrinsic activity might augment the anti-inflammatory activity of the NSAID, reduce its side effects or transform the potential therapeutic use from classical anti-inflammatory action to something else. Reports discussed in this review will be those of NO-NSAIDs, anticholinergic and AChEI-NSAIDs, Phospho-NSAIDs and some miscellaneous agents. In most cases, this review will cover literature dealing with these NSAID prodrugs from the year 2006 and later. Older literature will be used when necessary, e.g., to explain the chemical and biological mechanisms of action. PMID:23247285

  5. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  6. Effects of organophosphate pesticides and other drugs on subcortical mechanisms of visual integration.

    PubMed

    Revzin, A M

    1976-06-01

    Atropine, scopolamine, mevinphos, and eserine selectively block directional sensitivity of visual integrative neurones in the thalamus. Cholinergic drugs that do not penetrate the blood-brain barrier are without effect. The neurones studied are important links in reflex brain systems controlling visual attention and eye movements. The results suggest that any cholinergic drug that can get into the brain will disturb visual functions. Since the changes are qualitative and the system is reflex, the affected individual may be unaware of dysfunction. The resultant dangers to aerial applicator personnel are discussed, particularly with respect to atropine, which is necessary in the therapy of organophosphate and carbamate poisoning but is potentially harmful if self-administered for either pro-phylaxis or treatment.

  7. Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action.

    PubMed

    Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Piasecka, Anna; Kachlicki, Piotr; Kujawski, Radoslaw; Bogacz, Anna; Bartkowiak-Wieczorek, Joanna; Szulc, Michal; Kaminska, Ewa; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Gryszczynska, Agnieszka; Opala, Bogna; Lowicki, Zdzislaw; Seremak-Mrozikiewicz, Agnieszka; Czerny, Boguslaw

    2016-01-01

    Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration. PMID:27239217

  8. Anti-amnesic effect of alkaloid fraction from Lycopodiella cernua (L.) Pic. Serm. on scopolamine-induced memory impairment in mice.

    PubMed

    Chuong, Nguyen Ngoc; Trung, Bui Huu; Luan, Tran Cong; Hung, Tran Manh; Dang, Nguyen Hai; Dat, Nguyen Tien

    2014-07-11

    Lycopodiella cernua (L.) Pic. Serm. (Licopodiaceae) has been used in Vietnamese folk medicine for treating central nervous system conditions. In this study, the alkaloid fraction from the methanol extract of this plant (VLC) was evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity in cognition-relevant brain areas of mice. In in vivo study, the cognitive-enhancing effect of VLC on amnesic mice induced by scopolamine was investigated by assessing a passive avoidance and a Morris water maze test. VLC inhibited AChE activity in mouse frontal cortex, hippocampus and striatum with IC50 values of 26.7, 32.2 and 25.7μg/mL, respectively. Administration of VLC (10, 20, 50 and 100mg/kg, p.o.) significantly reversed cognitive impairments in mice by passive avoidance test. Treating with VLC (50mg/kg) reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P<0.05). These results indicated that L. cernua originated from Vietnam has anti-cholinesterase activity and might be useful for the treatment of cognitive impairment. PMID:24861508

  9. Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action

    PubMed Central

    Ozarowski, Marcin; Mikolajczak, Przemyslaw L.; Piasecka, Anna; Kachlicki, Piotr; Kujawski, Radoslaw; Bogacz, Anna; Bartkowiak-Wieczorek, Joanna; Szulc, Michal; Kaminska, Ewa; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Gryszczynska, Agnieszka; Opala, Bogna; Lowicki, Zdzislaw; Seremak-Mrozikiewicz, Agnieszka; Czerny, Boguslaw

    2016-01-01

    Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration. PMID:27239217

  10. Anti-amnesic effect of alkaloid fraction from Lycopodiella cernua (L.) Pic. Serm. on scopolamine-induced memory impairment in mice.

    PubMed

    Chuong, Nguyen Ngoc; Trung, Bui Huu; Luan, Tran Cong; Hung, Tran Manh; Dang, Nguyen Hai; Dat, Nguyen Tien

    2014-07-11

    Lycopodiella cernua (L.) Pic. Serm. (Licopodiaceae) has been used in Vietnamese folk medicine for treating central nervous system conditions. In this study, the alkaloid fraction from the methanol extract of this plant (VLC) was evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity in cognition-relevant brain areas of mice. In in vivo study, the cognitive-enhancing effect of VLC on amnesic mice induced by scopolamine was investigated by assessing a passive avoidance and a Morris water maze test. VLC inhibited AChE activity in mouse frontal cortex, hippocampus and striatum with IC50 values of 26.7, 32.2 and 25.7μg/mL, respectively. Administration of VLC (10, 20, 50 and 100mg/kg, p.o.) significantly reversed cognitive impairments in mice by passive avoidance test. Treating with VLC (50mg/kg) reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P<0.05). These results indicated that L. cernua originated from Vietnam has anti-cholinesterase activity and might be useful for the treatment of cognitive impairment.

  11. Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action.

    PubMed

    Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Piasecka, Anna; Kachlicki, Piotr; Kujawski, Radoslaw; Bogacz, Anna; Bartkowiak-Wieczorek, Joanna; Szulc, Michal; Kaminska, Ewa; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Gryszczynska, Agnieszka; Opala, Bogna; Lowicki, Zdzislaw; Seremak-Mrozikiewicz, Agnieszka; Czerny, Boguslaw

    2016-01-01

    Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.

  12. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  13. Drug Safety

    MedlinePlus

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  14. Two Distinct Types of Hypercontractile Esophagus: Classic and Spastic Jackhammer

    PubMed Central

    Hong, Yun Soo; Min, Yang Won; Rhee, Poong-Lyul

    2016-01-01

    Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Responses to treatments for jackhammer esophagus have been inconsistent in previous trials, possibly due to its heterogeneous manifestation. Thus, we reviewed 10 patients diagnosed with jackhammer esophagus and compared their clinical and manometric features at baseline. Additionally, manometric and symptomatic responses after treatment with known smooth muscle relaxants, including anticholinergic drugs (cimetropium bromide and scopolamine butylbromide) and a phosphodiesterase-5 inhibitor (sildenafil) were compared. We observed two distinct subgroups in the findings: one with hypercontractility and normal distal latencies (“classic jackhammer esophagus,” n=7) and the other with hypercontractility and short distal latencies (“spastic jackhammer esophagus,” n=3). The two types also differed in their responses to medications in that symptoms improved upon treatment with an anticholinergic agent in classic jackhammer esophagus patients, while spastic jackhammer esophagus was unresponsive to both the anticholinergic drugs and the phosphodiesterase-5 inhibitor. In conclusion, hypercontractile esophagus may be a heterogeneous disease with different underlying pathophysiologies. We introduced two novel terms, “classic jackhammer esophagus” and “spastic jackhammer esophagus,” to distinguish the two types. PMID:27458179

  15. Two Distinct Types of Hypercontractile Esophagus: Classic and Spastic Jackhammer.

    PubMed

    Hong, Yun Soo; Min, Yang Won; Rhee, Poong-Lyul

    2016-09-15

    Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Responses to treatments for jackhammer esophagus have been inconsistent in previous trials, possibly due to its heterogeneous manifestation. Thus, we reviewed 10 patients diagnosed with jackhammer esophagus and compared their clinical and manometric features at baseline. Additionally, manometric and symptomatic responses after treatment with known smooth muscle relaxants, including anticholinergic drugs (cimetropium bromide and scopolamine butylbromide) and a phosphodiesterase-5 inhibitor (sildenafil) were compared. We observed two distinct subgroups in the findings: one with hypercontractility and normal distal latencies ("classic jackhammer esophagus," n=7) and the other with hypercontractility and short distal latencies ("spastic jackhammer esophagus," n=3). The two types also differed in their responses to medications in that symptoms improved upon treatment with an anticholinergic agent in classic jackhammer esophagus patients, while spastic jackhammer esophagus was unresponsive to both the anticholinergic drugs and the phosphodiesterase-5 inhibitor. In conclusion, hypercontractile esophagus may be a heterogeneous disease with different underlying pathophysiologies. We introduced two novel terms, "classic jackhammer esophagus" and "spastic jackhammer esophagus," to distinguish the two types. PMID:27458179

  16. EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit

    PubMed Central

    Khan, M. Amer; Khan, M. Nematullah; Sultan, Ihtisham; Khan, M. Aamer; Ali, S. Amir; Farooqui, Afroze

    2015-01-01

    Introduction Inappropriate drug usage may preclude ideal benefit due to increased medical cost, antimicrobial resistance, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). Aim The present study was aimed at assessing the current drug practice and ADEs in COPD management in ICU. Materials and Methods A total of 1,044 patients admitted for the treatment of COPD were included in the study. Their prescriptions were recorded for evaluation of drug utilization and patients were counseled for assessing ADEs. Results were evaluated by Chi-square test and percentages. Result All-embracing 15,360 drugs were prescribed at an average of 14.71 drugs per patient, wherein β2-agonists were extensively prescribed agents followed by inhaled-corticosteroids and anti-cholinergics. 372 ADEs were reported in 252 patients, wherein restlessness was the most frequent ADE and theophylline was found to be associated with highest cases of ADEs. Conclusion Practitioners should prescribe least number of drugs to mitigate the likelihood of adverse outcomes in patients due to numerous drugs usage, which may be achieved by following GOLD guidelines. The present work may help in improving the current management of COPD by rectifying the flaws delineated in this article. PMID:26675667

  17. The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats.

    PubMed

    Sadek, Bassem; Khan, Nadia; Darras, Fouad H; Pockes, Steffen; Decker, Michael

    2016-10-15

    Both the acetylcholine esterase (AChE) and the histamine H3 receptor (H3R) are involved in the metabolism and modulation of acetylcholine release and numerous other centrally acting neurotransmitters. Hence, dual-active AChE inhibitors (AChEIs) and H3R antagonists hold potential to treat cognitive disorders like Alzheimer's disease (AD). The novel dual-acting AChEI and H3R antagonist 7-(3-(piperidin-1-yl)propoxy)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (UW-MD-72) shows excellent selectivity profiles over the AChE's isoenzyme butyrylcholinesterase (BChE) as well as high and balanced in-vitro affinities at both AChE and hH3R with IC50 of 5.4μM on hAChE and hH3R antagonism with Ki of 2.54μM, respectively. In the current study, the effects of UW-MD-72 (1.25, 2.5, and 5mg/kg, i.p.) on memory deficits induced by the muscarinic cholinergic antagonist scopolamine (SCO) and the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (DIZ) were investigated in a step-through type passive avoidance paradigm in adult male rats applying donepezil (DOZ) and pitolisant (PIT) as reference drugs. The results observed show that SCO (2mg/kg, i.p.) and DIZ (0.1mg/kg, i.p.) significantly impaired learning and memory in rats. However, acute systemic administration of UW-MD-72 significantly ameliorated the SCO- and DIZ-induced amnesic effects. Furthermore, the ameliorating activity of UW-MD-72 (1.25mg/kg, i.p.) in DIZ-induced amnesia was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10mg/kg, i.p.). Moreover, ameliorative effect of UW-MD-72 (1.25mg/kg, i.p.) in DIZ-induced amnesia was strongly reversed when rats were pretreated with a combination of ZOL (10mg/kg, i.p.) and SCO (1.0mg/kg, i.p.), indicating that these memory enhancing effects were, in addition to other neural circuits, observed through histaminergic H2R as well as

  18. Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

    PubMed

    Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

    2015-03-01

    Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia. PMID:25837935

  19. Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats.

    PubMed

    Yamazaki, Mayako; Okabe, Mayuko; Yamamoto, Noriyuki; Yarimizu, Junko; Harada, Katsuya

    2015-03-01

    Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%-50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia.

  20. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  1. Impact of drug administration route on drug delivery and distribution into the lung: an imaging mass spectrometry approach.

    PubMed

    Zecchi, Riccardo; Trevisani, Marcello; Pittelli, Maria; Pedretti, Pamela; Manni, Maria Elena; Pieraccini, Giuseppe; Pioselli, Barbara; Amadei, Francesco; Moneti, Gloriano; Catinella, Silvia

    2013-01-01

    During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has set a new frontier for the study of the distribution of endogenous and exogenous molecules present within a tissue. MALDI-IMS is a surface sampling technique that allows not only the detection of multiple analytes but also gives the spatial distribution of those analytes. Active compounds for pulmonary disease need an optimal and well-studied delivery into the lungs, in order to assure distribution with greater penetration into the peripheral or the alveolar region of the lung to maximize the therapeutic effects. IMS is very useful in the field of drug discovery, showing drug delivery and distribution in the body and organs. In this study, we present a comparison between two different ways of carrying out pulmonary drug administration: inhalation of a nebulized aerosol of aqueous drug solutions and intratracheal administration, which is much simpler, not expensive and commonly used during in vivo screening. Tiotropium bromide is a long-acting anticholinergic medicine used for maintenance treatment of chronic obstructive pulmonary disease. In the present work, tiotropium was administered by nebulization and by intratracheal instillation to guinea pigs at doses able to induce significant anti-bronchoconstrictive activity. Lung samples were dissected, frozen, cryosectioned and coated with matrix (α-hydroxy-cinnamic acid). IMS analyses were performed using a MALDI-LTQ-Orbitrap XL. Using this technique we were able to compare different distributions of the drug depending on the method of administration.

  2. Bushen-Yizhi formula ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in scopolamine-induced senescence in mice

    PubMed Central

    HOU, XUE-QIN; WU, DIAN-WEI; ZHANG, CHUN-XIA; YAN, RONG; YANG, CONG; RONG, CUI-PING; ZHANG, LEI; CHANG, XIANG; SU, RU-YU; ZHANG, SHI-JIE; HE, WEN-QING; QU, ZHAO; LI, SHI; SU, ZI-REN; CHEN, YUN-BO; WANG, QI; FANG, SHU-HUAN

    2014-01-01

    Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula consisting of six herbs has been reported to possess a neuroprotective effect. The present study aimed to investigate the effects of BSYZ on learning and memory abilities, as well as oxidative stress and neuronal apoptosis in the hippocampus of scopolamine (SCOP)-induced senescence in mice, in order to reveal whether BSYZ is a potential therapeutic agent for Alzheimer’s disease (AD). A high-performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of BSYZ. Extracts of BSYZ were orally administered to mice with SCOP-induced memory impairment for two weeks. The learning and memory abilities were determined by the Morris water maze test. The oxidant stress-related indices, such as activity of superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were examined in hippocampus of SCOP-treated mice. The cell death ratio was assessed by TUNEL staining, while apoptotic-related proteins including Bcl-2 and Bax were determined by immunofluorescent staining and western blot analysis. Caspase-3 was determined by western blot analysis. Consequently, a chromatographic condition, which was conducted at 35°C with a flow rate of 0.8 ml/min on the Gemini C18 column with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was established to yield common fingerprint chromatography under 203 nm with a similarity index of 0.986 within 10 batches of BSYZ samples. BSYZ at a dose of 2.92 g/kg significantly improved the cognitive ability, restored the abnormal activity of SOD and increased the levels of MDA and GSH induced by SCOP. Moreover, the neural apoptosis in the hippocampus of SCOP-treated mice was reversed by BSYZ by regulating the expression of Bcl-2, Bax and caspase-3. The results demonstrated that BSYZ had neuroprotective effects in SCOP-induced senescence in mice by ameliorating oxidative stress and neuronal apoptosis in the

  3. Effects of anaesthesia techniques and drugs on pulmonary function.

    PubMed

    Saraswat, Vijay

    2015-09-01

    The primary task of the lungs is to maintain oxygenation of the blood and eliminate carbon dioxide through the network of capillaries alongside alveoli. This is maintained by utilising ventilatory reserve capacity and by changes in lung mechanics. Induction of anaesthesia impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics. All drugs used during anaesthesia, including inhalational agents, affect pulmonary functions directly by acting on respiratory system or indirectly through their actions on other systems. Volatile anaesthetic agents have more pronounced effects on pulmonary functions compared to intravenous induction agents, leading to hypercarbia and hypoxia. The posture of the patient also leads to major changes in pulmonary functions. Anticholinergics and neuromuscular blocking agents have little effect. Analgesics and sedatives in combination with volatile anaesthetics and induction agents may exacerbate their effects. Since multiple agents are used during anaesthesia, ultimate effect may be different from when used in isolation. Literature search was done using MeSH key words 'anesthesia', 'pulmonary function', 'respiratory system' and 'anesthesia drugs and lungs' in combination in PubMed, Science Direct and Google Scholar filtered by review and research articles sorted by relevance. PMID:26556914

  4. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  5. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  6. PRN prescribing in psychiatric inpatients: potential for pharmacokinetic drug interactions.

    PubMed

    Davies, Simon J C; Lennard, Martin S; Ghahramani, Parviz; Pratt, Peter; Robertson, Andrea; Potokar, John

    2007-03-01

    Medications are commonly prescribed to psychiatric inpatients on a PRN (pro re nata/as required) basis, allowing drugs to be administered on patient request or at nurses' discretion for psychiatric symptoms, treatment side effects or physical complaints. However, there has been no formal study of the pharmacokinetic implications of PRN prescribing. The objective of the study was to determine the prevalence of PRN drug prescription and administration, and to assess the potential for interactions involving CYP2D6 and CYP3A4 between drugs prescribed and administered to inpatients on psychiatry wards.A cross-sectional survey of prescriptions on general adult and functional elderly psychiatric wards in one city was carried out. Data were recorded from prescription charts of 323 inpatients (236 on general adult and 87 on functional elderly wards). Of 2089 prescriptions, 997 (48%) of prescriptions were on a PRN basis (most commonly benzodiazepines and other hypnotic agents, antipsychotics, analgesics and anticholinergic agents), but only 143 (14%) of these had been administered in the previous 24 hours. One fifth of patients were prescribed drug combinations interacting with CYP2D6 or CYP3A4 of potential clinical importance which included one or more drugs prescribed on a PRN basis.PRN prescribing is common among inpatients in psychiatry, and may lead to cytochrome P450 mediated interactions. Prescribers should be aware of the potential for unpredictability in plasma concentrations, side effects and efficacy which PRN prescribing may cause through these interactions, particularly in old age psychiatry and in treatment of acute psychosis.

  7. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  8. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-07-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing.

  9. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  10. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  11. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  12. [Treatment with tianeptine of depressive disorders in drug addicts under withdrawal. Assessment of efficacy and study of dependence].

    PubMed

    Lôo, H; Hantzberg, P; Defrance, R; Kamoun, A; Deniker, P

    1987-01-01

    The study concerns the use of a new antidepressant, tianeptine, as a treatment of depressive and/or amotival syndrome, in 30 drug addicts, detoxified from opiates. From a thymoanaleptic point of view, 85% of the patients exhibit a positive result after 28 days of treatment with 37.5 mg/day. These good results are confirmed by the evolution of the Hamilton Depression Rating Scale global score, which significantly decreases from D0 to D14 and from D14 to D28. The acceptability of the antidepressant is good. Anticholinergic side-effects are very uncommon. Tianeptine appears devoid of any obvious psychostimulant or sedative effect. The drug compliance, estimated by counting the tablets, is very satisfying: there is no tendency to a spontaneous increase of dosing. The follow-up of the patients after drug cessation has not shown any symptoms suggesting psychological or physical dependence towards the drug. During this study in subjects particularly predisposed to the abuse of psychoactive drugs, tianeptine has not induced anything suggesting the possibility of drug abuse or tolerance.

  13. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  14. Therapeutic potential of histaminergic compounds in the treatment of addiction and drug-related cognitive disorders.

    PubMed

    Alleva, Livia; Tirelli, Ezio; Brabant, Christian

    2013-01-15

    Addiction is a behavioral disorder characterized by the compulsive seeking and taking of drugs despite serious negative consequences. In particular, the chronic use of drugs impairs memory and cognitive functions, which aggravates the loss of control over drug use and complicates treatment outcome. Therefore, cognitive enhancers targeting acetylcholine have been proposed to treat addiction. Interestingly, histamine H(3) receptor (H(3)R) antagonists/inverse agonists stimulate acetylcholine transmission in different brain areas, facilitate memory in animal models and can reverse learning deficits induced by drugs such as scopolamine, dizocilpine and alcohol. Moreover, several studies found that compounds capable of activating the histaminergic system generally decrease the reinforcing effects of drugs, namely alcohol and opioids, in preclinical models of addiction. Finally, several H(3)R antagonists/inverse agonists increase histamine in the brain and have proven to be safe in humans. However, no studies have yet investigated the therapeutic potential of cognitive enhancing H(3)R antagonists/inverse agonists in the treatment of addiction in humans. The present review first describes the impact of addictive drugs on learning processes and cognitive functions that play an important role for addicts to remain abstinent. Second, our work briefly summarizes the relevant literature describing the function of histamine in learning, memory and drug addiction. Finally, the potential therapeutic use of histaminergic agents in the treatment of addiction is discussed. Our review suggests that histaminergic compounds like H(3)R antagonists/inverse agonists may improve the treatment outcome of addiction by reversing drug-induced cognitive deficits and/or diminishing the reinforcing properties of addictive drugs, especially opioids and alcohol.

  15. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  16. Efficacy of phosphatidylcholine in the modulation of motion sickness susceptibility

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Ryan, P.; Homick, J. L.

    1985-01-01

    This study evaluated the efficacy of pharmacological doses of phosphatidylcholine (lecithin) in the modulation of motion sickness induced by exposure to coriolis stimulation in a rotating chair. Subjects received daily dietary supplements of 25 grams of lecithin (90 percent phosphatidylcholine) and were tested for their susceptibility to motion sickness after 4 h, 2 d, and 21 d. A small but statistically significant increase in susceptibility (+15 percent) was noted 4 h after supplemental phosphatidylcholine, with four of nine subjects demonstrating a marked increase in susceptibility. This finding was attributed to choline's stimulatory action on cholinergic systems, an action which opposes that of the classical antimotion sickness drug scopolamine. Chronic lecithin loading revealed a trend towards reduced susceptibility, possibly indicating the occurrence of adaptive mechanisms such as receptor down-regulation. Withdrawal from lecithin loading, perhaps coupled with anticholinergic treatment, might prove to be a potent prophylactic regimen and ought to be tested.

  17. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  18. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  19. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  20. Prenatal exposure to anti-HIV drugs. long-term neurobehavioral effects of lamivudine (3TC) in CD-1 mice.

    PubMed

    Calamandrei, G; Venerosi, A; Branchi, I; Valanzano, A; Alleva, E

    2000-01-01

    The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (NaCl 0. 9%) from pregnancy day 10 to delivery. Offspring behavior was examined on postnatal day 35 in a 20-min social interaction test. At adulthood different behavioral endpoints were analyzed, including locomotor activity and exploration in an open field following administration of the muscarinic antagonist scopolamine (2 mg/kg), spatial learning in either radial arm or Morris water maze, virgin female behavior in a maternal induction test, and pain sensitivity in a hot-plate test (52 +/- 0.1 degrees C). Our findings confirm the low neurotoxicity of 3TC in comparison to AZT. However some significant behavioral alterations were found, namely (1) a decrease in immobility in the open field test, (2) an increase in the responsiveness to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in the open field, and (3) a longer escape latency in the first day of the reversal phase in the Morris task (particularly marked in the 250-mg/kg treatment group). No significant changes in either pain sensitivity, social/affiliative, or maternal behavior were found, although a higher occurrence of aggressive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females.

  1. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  2. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  3. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  4. Drug Reactions

    MedlinePlus

    ... or diabetes. But medicines can also cause unwanted reactions. One problem is interactions, which may occur between ... more serious. Drug allergies are another type of reaction. They can be mild or life-threatening. Skin ...

  5. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  6. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  7. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  8. Club Drugs

    MedlinePlus

    ... also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known ...

  9. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  10. Drug misuse.

    PubMed Central

    Waller, T.

    1992-01-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  11. A review of drug-induced acute angle closure glaucoma for non-ophthalmologists

    PubMed Central

    Ah-kee, Elliott Yann; Egong, Eric; Shafi, Ahad; Lim, Lik Thai; Yim, James Li

    2015-01-01

    Acute angle closure glaucoma is an ophthalmic emergency and can lead to blindness if left untreated. Several types of drugs have the potential to precipitate acute angle closure glaucoma. These include adrenergic, cholinergic and anticholinergic, antidepressants, anticoagulants and sulfa-based agents. This article provides a basic overview of the risk factors and pathophysiologic mechanisms involved in angle closure glaucoma and focuses on drug-induced angle closure glaucoma for the non-ophthalmologist. A PubMed search limited to the English language was conducted to find relevant literature for the purpose of this article. Most attacks occur in subjects unaware that they are at risk due to innately narrow iridocorneal angles. Clinicians should always review medications in patients presenting with symptoms of acute angle closure glaucoma. The aim of this article is to bring this ophthalmic condition to the attention of clinicians, particularly those outside the field of ophthalmology who commonly prescribe these medications or see these patients prior to referring to ophthalmologists. PMID:26535174

  12. A review of drug-induced acute angle closure glaucoma for non-ophthalmologists.

    PubMed

    Ah-Kee, Elliott Yann; Egong, Eric; Shafi, Ahad; Lim, Lik Thai; Yim, James Li

    2015-01-01

    Acute angle closure glaucoma is an ophthalmic emergency and can lead to blindness if left untreated. Several types of drugs have the potential to precipitate acute angle closure glaucoma. These include adrenergic, cholinergic and anticholinergic, antidepressants, anticoagulants and sulfa-based agents. This article provides a basic overview of the risk factors and pathophysiologic mechanisms involved in angle closure glaucoma and focuses on drug-induced angle closure glaucoma for the non-ophthalmologist. A PubMed search limited to the English language was conducted to find relevant literature for the purpose of this article. Most attacks occur in subjects unaware that they are at risk due to innately narrow iridocorneal angles. Clinicians should always review medications in patients presenting with symptoms of acute angle closure glaucoma. The aim of this article is to bring this ophthalmic condition to the attention of clinicians, particularly those outside the field of ophthalmology who commonly prescribe these medications or see these patients prior to referring to ophthalmologists.

  13. Thyroid-Induced Worsening of Parkinsonian Tremor Resistant to Drugs and Subthalamic Nucleus Deep Brain Stimulation

    PubMed Central

    Minár, Michal; Valkovič, Peter

    2014-01-01

    Introduction. Symptoms of both hypothyroidism and thyrotoxicosis can be easily overlooked in patients with Parkinson's disease (PD). We report on a patient whose parkinsonian tremor worsened and proved refractory not only to common treatment, but also to deep brain stimulation (DBS). Case Presentation. A 61-year-old woman with advanced PD underwent bilateral subthalamic DBS, with an excellent outcome. Twenty-one months after the surgery, however, patient's resting/postural tremor markedly worsened. There was a slight improvement for 1 month after repeated adjustments of DBS parameters, but then the tremor worsened again. Since even a minimal increase of the dose of dopaminergic drugs caused extremely severe dyskinesias, an anticholinergic drug biperiden and benzodiazepine clonazepam were introduced, what helped for another month. With the onset of severe diarrhoea, a laboratory workup was performed. Thyrotoxicosis was detected. During treatment with the antithyroid agent carbimazole, the parkinsonian tremor clearly improved within two weeks. Conclusion. A hyperthyroid state can markedly exaggerate all forms of tremor, as well as other types of movement disorders. This condition can be overlooked or masked by other symptoms. Therefore, if the tremor in a patient with PD gradually worsens and proves resistant to the usual treatment, examine the thyroid gland. PMID:25628904

  14. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided.

  15. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  16. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated.

  17. Pharmacological evaluation of 2-(4-methylaminobutoxy)diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug with antidepressant activity.

    PubMed

    Tobe, A; Yoshida, Y; Ikoma, H; Tonomura, S; Kikumoto, R

    1981-01-01

    Pharmacological properties of 2-(4-methylamino-butoxy)-diphenylmethane hydrochloride (MCI-2016) were examined in comparison with those of other antidepressants. MCI-2016 significantly antagonized the hypothermia and depression-like syndrome produced by reserpine injection. Furthermore, the drug exhibited such activities as antitetrabenazine and anti-cataleptic actions, and potentiation of the behavioural excitation induced by yohimbine, methamphetamine and L-dopa. MCI-2016 showed a definite suppressive effect on muricidal activity in olfactory bulb removed rats and the long-term isolation-induced fighting in mice without causing apparent motor disturbance. Judging from the effects of the drug on in vitro response to noradrenaline (NA) and serotonin (5-HT), and on p-chloramphetamine-induced hypermotility, it is suggested that MCI-2016 is a selective potentiator of NA presumably due to an inhibition of NA uptake. Anticholinergic and sedative actions of MCI-2016 were considerably weaker than those of amitriptyline and imipramine. Acute toxicity of MCI-2016 was the weakest among the drugs tested. These pharmacological profiles may suggest a potential clinical utility of MCI-2016 as a new psychotropic agent having an antidepressant activity.

  18. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  19. Motor activity-induced dopamine release in the substantia nigra is regulated by muscarinic receptors.

    PubMed

    Andersson, Daniel R; Björnsson, Evelina; Bergquist, Filip; Nissbrandt, Hans

    2010-01-01

    Nigro-striatal neurons release dopamine not only from their axon terminals in the striatum, but also from somata and dendrites in the substantia nigra. Somatodendritic dopamine release in the substantia nigra can facilitate motor function by mechanisms that may act independently of axon terminal dopamine release in the striatum. The dopamine neurons in the substantia nigra receive a cholinergic input from the pedunculopontine nucleus. Despite recent efforts to introduce this nucleus as a potential target for deep brain stimulation to treat motor symptoms in Parkinson's disease; and the well-known antiparkinsonian effects of anticholinergic drugs; the cholinergic influence on somatodendritic dopamine release is not well understood. The aim of this study was to investigate the possible regulation of locomotor-induced dopamine release in the substantia nigra by endogenous acetylcholine release. In intact and 6-OHDA hemi-lesioned animals alike, the muscarinic antagonist scopolamine, when perfused in the substantia nigra, amplified the locomotor-induced somatodendritic dopamine release to approximately 200% of baseline, compared to 120-130% of baseline in vehicle-treated animals. A functional importance of nigral muscarinic receptor activation was demonstrated in hemi-lesioned animals, where motor performance was significantly improved by scopolamine to 82% of pre-lesion performance, as compared to 56% in vehicle-treated controls. The results indicate that muscarinic activity in the substantia nigra is of functional importance in an animal Parkinson's disease model, and strengthen the notion that nigral dopaminergic regulation of motor activity/performance is independent of striatal dopamine release.

  20. Possible role for anisodamine in organophosphate poisoning.

    PubMed

    Eisenkraft, Arik; Falk, Avshalom

    2016-06-01

    In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison-directed antidotes, patients may require extra oxygen and artificial ventilation; other modalities may also be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs from this family is non subtype-selective muscarinic, and a nicotinic cholinoceptor antagonist, which has been employed in traditional Chinese medicine. As a muscarinic antagonist, it displays similar pharmacological effects to atropine and scopolamine. However, anisodamine is not only less potent than atropine and scopolamine but also less toxic. Current in vitro and animal model studies have demonstrated that anisodamine has protective effects in a variety of diseases. Organophosphate poisoning involves not only the central and peripheral nervous systems, but also the cardiac and respiratory systems, as well as activation of inflammatory processes and oxidative stress. Therefore, the anticholinergic and additional activities of anisodamine appear to be relevant and justify its consideration as an addition to the existing remedies. However, more research is needed, as at present data on the role of anisodamine in the management of organophosphate poisoning are limited. Here, we review the beneficial effects of anisodamine on processes relevant to organophosphate poisoning.

  1. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

  2. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

  3. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Current research findings and treatment issues related to a number of drugs are briefly outlined. Topics include T-20, a reformulation of ddI, PMPA, chicoric acid, Omniferon (alpha leukoferon), and Mepron. Also discussed is a non-nucleoside reverse transcriptase inhibitor called calanolide A, which is synthesized from a tree native to Malaysian rain forests. An update is provided on Panretin, a gel which is used to treat KS lesions. Contact information is provided.

  4. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  5. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  6. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  7. Drugs Approved for Neuroblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  8. Drugs Approved for Retinoblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  9. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  10. Drug Plan Coverage Rules

    MedlinePlus

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  11. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  12. [Drug poisoning].

    PubMed

    Gainza, I; Nogué, S; Martínez Velasco, C; Hoffman, R S; Burillo-Putze, G; Dueñas, A; Gómez, J; Pinillos, M A

    2003-01-01

    A review is made of acute poisoning by opiates and its treatment in the emergency services, bearing in mind the progressive decline in the number of cases presented with the arrival of new forms of their administration, as well as the presence of new addictive drugs that have resulted in a shift in consumption habits. Reference is also made to the way in which the different types of existing substances originated, with the aim of achieving a better understanding of their use and in order to administer the most suitable treatment when poisoning occurs. Cocaine poisoning is discussed, with reference to its clinical picture, diagnosis and treatment. The consumption of illegal drugs in our country has undergone a notable change in recent years, with heroin being relegated and the incorporation of cocaine, amphetamine derivatives such as "ecstasy" (MDMA), "liquid ecstasy" (GHB) and, to a lesser extent, ketamine. A review is made of cannabis and its derivates, from the history of its consumption and the preparations employed to the effects produced in the different bodily systems. A brief explanation is also given of its metabolites and its principal mechanisms of action. Finally, we comment on the effects of LSD and hallucinogenic mushrooms.

  13. Drugs and the Brain.

    ERIC Educational Resources Information Center

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  14. Measuring drug saturation solubility in thin polymer films: use of a thin acceptor layer.

    PubMed

    Kunst, Anders; Lee, Geoffrey

    2015-03-15

    The saturation solubility of scopolamine base in two pressure sensitive adhesive DURO-TAKs has been determined using the 5-layer laminate technique. The acceptor layer had a thickness of less than 25 μm to promote a rapid partitioning equilibrium. With DURO-TAK 87-2510 the saturation solubility is 5.2 ± 0.6% w/w when measured after 7 days. With DURO-TAK 87-4098 the saturation solubility is slightly higher, 7.9 ± 0.7% w/w after 7 days. These values remained constant up to approximately 30 days' experimental time. In both cases the acceptor was free of crystalline material at the end of the experiment. This strongly suggests that that equilibrium had been reached between the saturated solution in the acceptor layer and the crystalline drug still present in the donor layer. The addition of light liquid paraffin to the acceptor produced a solubilizing effect with 87-4098 but not 87-2510. We recommend some experimental conditions that we consider to be necessary to achieve a reliable and accurate result with this technique. If performed correctly, it can give a feasible result.

  15. Effects of antiepileptic drugs on learning as assessed by a repeated acquisition of response sequences task in rats.

    PubMed

    Shannon, Harlan E; Love, Patrick L

    2007-02-01

    Patients with epilepsy can have impaired cognitive abilities. Antiepileptic drugs (AEDs) may contribute to the cognitive deficits observed in patients with epilepsy, and have been shown to induce cognitive impairments in healthy individuals. However, there are few systematic data on the effects of AEDs on specific cognitive domains. We have previously demonstrated that a number of AEDs can impair working memory and attention. The purpose of the present study was to evaluate the effects of AEDs on learning as measured by a repeated acquisition of response sequences task in nonepileptic rats. The GABA-related AEDs phenobarbital and chlordiazepoxide significantly disrupted performance by shifting the learning curve to the right and increasing errors, whereas tiagabine and valproate did not. The sodium channel blockers carbamazepine and phenytoin suppressed responding at higher doses, whereas lamotrigine shifted the learning curve to the right and increased errors, and topiramate was without significant effect. Levetiracetam also shifted the learning curve to the right and increased errors. The disruptions produced by triazolam, chlordiazepoxide, lamotrigine, and levetiracetam were qualitatively similar to the effects of the muscarinic cholinergic receptor antagonist scopolamine. The present results indicate that AEDs can impair learning, but there are differences among AEDs in the magnitude of the disruption in nonepileptic rats, with drugs that enhance GABA receptor function and some that block sodium channels producing the most consistent impairment of learning. PMID:17174158

  16. Clinically significant drug interactions.

    PubMed

    Ament, P W; Bertolino, J G; Liszewski, J L

    2000-03-15

    A large number of drugs are introduced every year, and new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely on memory alone to avoid potential drug interactions. Multiple drug regimens carry the risk of adverse interactions. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. Regularly updated manuals of drug interactions and CD-ROM-formatted programs are useful office references. PMID:10750880

  17. Personality, Drug Preference, Drug Use, and Drug Availability

    ERIC Educational Resources Information Center

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  18. 99 Films on Drugs.

    ERIC Educational Resources Information Center

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  19. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  20. Attitudes towards drug legalization among drug users.

    PubMed

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  1. Drug Use by Students of Drug Abuse

    ERIC Educational Resources Information Center

    Linder, Ronald; And Others

    1973-01-01

    The purpose of this study was to determine the significance of differences in the use of certain psychoactive drugs among students who enrolled for an elective drug abuse course and students not enrolled, or who have not previously taken a drug abuse course. (Author)

  2. Discontinued drugs in 2008: cardiovascular drugs.

    PubMed

    Zhang, Xu-Song; Xiang, Bing-Ren

    2009-07-01

    This perspective is part of an annual series of papers discussing drugs dropped from clinical development in the previous year. Specifically, this paper focuses on the 16 cardiovascular drugs discontinued in 2008. Information for this perspective was derived from a search of the Pharmaprojects database for drugs discontinued after reaching Phase I-III clinical trials. PMID:19548849

  3. Access to Investigational Drugs

    MedlinePlus

    ... drug if the supply is limited and the demand is high. Are all investigational drugs available through ... be limited in part by drug supply, patient demand, or other factors. What is NCI’s role in ...

  4. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  5. Drugs Approved for Leukemia

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  6. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  7. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  8. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  9. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  10. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  11. Donepezil: an important prototype to the design of new drug candidates for Alzheimer's disease.

    PubMed

    Rodrigues Simões, Maria Cecilia; Dias Viegas, Flávia Pereira; Moreira, Marcella Soares; de Freitas Silva, Matheus; Riquiel, Mariana Máximo; da Rosa, Patrícia Mattos; Castelli, Maísa Rosa; dos Santos, Marcelo Henrique; Soares, Marisi Gomes; Viegas, Claudio

    2014-01-01

    Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder, with a dramatic socioeconomic impact. The progress of AD is characterized by a severe loss in memory and cognition, leading to behavioral changing, depression and death. During the last decades, only a few anticholinergic drugs were launched in the market, mainly acetylcholinesterase inhibitors (AChEIs), with indications for the treatment of initial and moderate stages of AD. The search for new AChEIs, capable to overcome the limitations observed for rivastigmine and tacrine, led Sugimoto and co-workers to the discovery of donepezil. Besides its high potency, donepezil also exhibited high selectivity for AChE and a very low toxicity. In this review, we discuss the main structural and pharmacological attributes that have made donepezil the first choice medicine for AD, and a versatile structural model for the design of novel AChEIs, in spite of multipotent and multitarget-directed ligands. Many recent data from literature transdue great efforts worldwide to produce modifications in the donepezil structure that could result in new bioactive chemical entities with innovative structural pattern. Furthermore, multi-potent ligands have also been designed by molecular hybridization, affording rivastigmine-, tacrine- and huperzine-donepezil potent and selective AChEIs. In a more recent strategy, structural features of donepezil have been used as a model to design multitarget-directed ligands, aiming at the discovery of new effective drug candidates that could exhibit concomitant pharmacological activities as dual or multi- enzymatic inhibitors as genuine innovative therapeutic alternatives for the treatment of AD.

  12. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR), due to transactivation of xenobiotic-response elements (XREs) present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification) facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP) and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs) on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome) of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug’s impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse models and

  13. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan Lundine); "Patience and…

  14. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  15. Drugs and Young People

    MedlinePlus

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  16. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  17. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  18. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID:22043389

  19. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  20. Do drug offences matter?

    PubMed

    Gordon, A M

    1978-07-15

    Drug offences in addicts are often thought to indicate little more than continued dependency. In a four-year follow-up study of 60 men attending a drug clinic a history of repeated convictions for drug offences was found to be strongly related to patterns of delinquency. The following variables were associated with a history of repeated drug offences: a higher conviction rate for "non-drug" offences; younger age at first conviction; conviction preceding drug use; convictions for offences of sex and violence; longer prison sentences; and regular narcotic use and continued dependency at follow-up. Receiving a clinic prescription was not associated with a lower incidence of drug offences. Repeated drug offences identified a subgroup of drug users who were characterised by extensive sociopathic behaviour. Such offences should not be dismissed as an unavoidable, unimportant part of addiction. PMID:678840

  1. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions." PMID:16412107

  2. Discontinued drugs in 2010: cardiovascular drugs.

    PubMed

    Zhao, Hong-ping; Zhang, Xu-song; Xiang, Bing-ren

    2011-10-01

    This perspective is a paper discussing drugs dropped from clinical development in the previous years. Specifically, this paper focuses on 16 cardiovascular drugs discontinued in 2010 after reaching Phase I - III clinical trials. Information for this perspective is mainly derived from a search of Pharmaprojects. PMID:21870899

  3. [Psychiatric drugs as risk factor in fatal heat stroke].

    PubMed

    Fijnheer, R; van de Ven, P J; Erkelens, D W

    1995-07-01

    Two men aged 33 and 31 years suffered a fatal heat stroke on a warm summer day. One of them used pimozide and clomipramine, the other zuclopenthixol, dexetimide, droperidol, promethazine and propranolol as psychiatric medication. Both of them had a body temperature > 42.3 degrees C, without perspiring. At first only a comatose situation with practically normal laboratory values existed; this was rapidly followed by massive liver damage, disseminated intravascular coagulation, anaemia, thrombopenia and acute renal failure. In spite of adequate and rapid treatment these complications were fatal. Both patients used medication with an antidopaminergic and anticholinergic (side) effect. The set point of the temperature regulation centre can be elevated by the antidopaminergic activity of antipsychotics. Use of anticholinergic medication can disturb the thermoregulation via inhibition of the parasympathicomimetically mediated sweat secretion. It is recommended to point out the danger of unusually high outdoor temperatures to patients using this medication. PMID:7617062

  4. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices.

  5. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  6. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  7. Antidiarrheal drug overdose

    MedlinePlus

    ... class of drugs that includes morphine and other narcotics. Use of prescription opioids for nonmedical reasons is ... tracing) Intravenous fluids (given through a vein) Laxative Narcotic-counteracting drug (antagonist), approximately every 30 minutes Tube ...

  8. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  9. The Drug Education Gap

    ERIC Educational Resources Information Center

    Reynolds, John C., Jr.

    1976-01-01

    Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)

  10. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  11. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  12. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process.

  13. Animal Drug Safety FAQs

    MedlinePlus

    ... the top How do you determine if a veterinary drug is safe to market? As mandated by the ... to the top How does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal ...

  14. Drug Interaction and Pharmacist

    PubMed Central

    Ansari, JA

    2010-01-01

    The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. PMID:21042495

  15. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include narcotic painkillers, ...

  16. Treating Prescription Drug Addiction

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... View all ​Research Reports Opioids: The Prescription Drug & Heroin Overdose Epidemic (HHS website) NIDA Home Site Map ...

  17. Black Youths and Illegal Drugs.

    ERIC Educational Resources Information Center

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  18. Contemporary drugs of abuse.

    PubMed

    Giannini, A J; Price, W A; Giannini, M C

    1986-03-01

    The physician needs to know the signs, symptoms and recommended treatments of drug overdoses. Overdose of hallucinogens usually does not require drug therapy. Overdose of amphetamines ("uppers") may be complicated by the presence of PCP, a dissociative substance. It is important for the physician to be familiar with the street terminology for contemporary drugs of abuse and to be aware of how users obtain these drugs.

  19. Polypharmacology in a single drug: multitarget drugs.

    PubMed

    Bolognesi, M L

    2013-01-01

    Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal.

  20. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  1. Educating against Drug Abuse.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This book is a compilation of drug education and drug abuse prevention materials collected by United Nations Educational, Scientific and Cultural Organization (UNESCO) along with example of activities carried out by various countries. It opens with four introductory papers by separate authors: (1) "Prevention of Drug Dependence: A Utopian Dream?"…

  2. Other Drugs of Abuse

    MedlinePlus

    ... can make you pass out. It's called a "date rape" drug because someone can secretly put it in your ... you without your permission. Rohypnol (roofies) is a date rape pill and can ... about these drugs . Bath Salts are drugs made with chemicals like ...

  3. Strategies against Drugs.

    ERIC Educational Resources Information Center

    Metzler, Birgit

    1996-01-01

    The main private organization in Germany dedicated to combatting drug addition--the DHS and the Federal Health Information Agency (BzGA) jointly estimate the number of persons addicted to "illegal" drugs in Germany at around 200,000. Yet, people may grow up immune to drug addiction if they acquire a stable basis for self-confidence and…

  4. Keeping Youth Drug Free.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This guide is designed to help caregivers prevent children from getting involved in drugs. It details six key prevention principles, including actions caregivers can take that can help their child make healthy choices. Each section includes language to use with children, activities to do, information about drugs, statistics about youth drug use,…

  5. Drugs and the Coach.

    ERIC Educational Resources Information Center

    Clarke, Kenneth S., Ed.

    This volume is based on the premise that professional preparation for coaching should include viable experiences in drug education, with particular reference to coping with drug-related problems. The first section provides general information on the purposes and effects of drugs, controls, and concepts of doping. The second section deals with four…

  6. Drugs of Abuse.

    ERIC Educational Resources Information Center

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  7. Anticholinergic therapy for overactive bladder: a nicotinic modality?

    PubMed

    Toler, Steven M; Yohannes, Daniel; Lippiello, Patrick M; Chancellor, Michael B

    2013-09-01

    Until recently the treatment of Overactive Bladder (OAB) has primarily been aimed at mitigating hypercholinergic activity in the bladder via antagonism of muscarinic acetylcholine receptors. However, antimuscarinic therapies have limited efficacy and significant side effects. It is now known that nicotinic acetylcholine receptor (nAChR) subtypes are expressed in the urothelium and on afferent nerve fibers in the bladder, and it is believed that these receptors serve to communicate urgency and facilitate voiding function. This presents the opportunity for an alternative to the antimuscarinic approach, one which involves inhibition of nAChRs in the bladder that are chronically overstimulated by acetylcholine. Specifically, we hypothesize that an orally administered nAChR-selective inhibitor with extensive renal elimination will result in higher local concentrations in the bladder and lower systemic exposure than current therapies, representing a novel targeted approach to the treatment of OAB with a more favorable side effect profile.

  8. Actions of cholinergic drugs in the nematode Ascaris suum. Complex pharmacology of muscle and motorneurons

    PubMed Central

    1993-01-01

    The cholinergic agonists acetylcholine (ACh), nicotine, and pilocarpine produced depolarizations and contractions of muscle of the nematode Ascaris suum. Dose-dependent depolarization and contraction by ACh were suppressed by about two orders of magnitude by 100 microM d- tubocurarine (dTC), a nicotinic antagonist, but only about fivefold by 100 microM N-methyl-scopolamine (NMS), a muscarinic antagonist. NMS itself depolarized both normal and synaptically isolated muscle cells. The muscle depolarizing action of pilocarpine was not consistently antagonized by either NMS or dTC. ACh receptors were detected on motorneuron classes DE1, DE2, DI, and VI as ACh-induced reductions in input resistance. These input resistance changes were reversed by washing in drug-free saline or by application of dTC. NMS applied alone lowered input resistance in DE1, but not in DE2, DI, or VI motorneurons. In contrast to the effect of ACh, the action of NMS in DE1 was not reversed by dTC, suggesting that NMS-sensitive sites may not respond to ACh. Excitatory synaptic responses in muscle evoked by depolarizing current injections into DE1 and DE2 motorneurons were antagonized by dTC; however, NMS antagonized the synaptic output of only the DE1 and DE3 classes of motorneurons, an effect that was more likely to have been produced by motorneuron conduction failure than by pharmacological blockade of receptor. The concentration of NMS required to produce these changes in muscle polarization and contraction, ACh antagonism, input resistance reduction, and synaptic antagonism was 100 microM, or more than five orders of magnitude higher than the binding affinity for [3H]NMS in larval Ascaris homogenates and adult Caenorhabditis elegans (Segerberg, M. A. 1989. Ph.D. thesis. University of Wisconsin-Madison, Madison, WI). These results describe a nicotinic- like pharmacology, but muscle and motorneurons also have unusual responses to muscarinic agents. PMID:8455017

  9. Drug companies, UNAIDS make drugs available.

    PubMed

    1998-01-01

    The United Nations AIDS (UNAIDS) initiative is working with several drug companies and four countries on a pilot program to build a health infrastructure that provides affordable drugs to insure that combination therapies are used appropriately. The countries involved in the program are Uganda, Chile, Vietnam and Cote d'Ivoire, and the drug companies are Glaxo Wellcome, Hoffmann-La Roche, and Virco NV. Each country agreed to form national HIV/AIDS drug advisory boards, and non-profit companies will act as clearinghouses. Financing will come from the pharmaceutical companies, local health ministries, and a $1 million grant from UNAIDS. The program will be evaluated in terms of improvements to overall health care delivery, number of people treated, the impact on emergency care, and the rate of illness and death.

  10. Drug Rash (Unclassified Drug Eruption) in Adults

    MedlinePlus

    ... microscope by a specially trained physician (dermatopathologist). In addition, your doctor may want to perform blood work to look for signs of an allergic reaction. The best treatment for a drug rash is ...

  11. Drug abuse and addiction.

    PubMed

    Nessa, A; Latif, S A; Siddiqui, N I; Hussain, M A; Hossain, M A

    2008-07-01

    Among the social and medical ills of the twentieth century, substance abuse ranks as on one of the most devastating and costly. The drug problem today is a major global concern including Bangladesh. Almost all addictive drugs over stimulate the reward system of the brain, flooding it with the neurotransmitter dopamine. That produces euphoria and that heightened pleasure can be so compelling that the brain wants that feeling back again and again. However repetitive exposure induces widespread adaptive changes in the brain. As a consequence drug use may become compulsive. An estimated 4.7% of the global population aged 15 to 64 or 184 million people, consume illicit drug annually. Heroin use alone is responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug addicted infant born each year. Department of narcotic control (DNC) in Bangladesh reported in June 2008 that about 5 million drug addicts in the country & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these drug addicts, 91% are young and adolescents population. Heroin is the most widely abused drugs in Bangladesh. For geographical reason like India, Pakistan and Myanmar; Bangladesh is also an important transit root for internationally trafficking of illicit drug. Drug abuse is responsible for decreased job productivity and attendance increased health care costs, and escalations of domestic violence and violent crimes. Drug addiction is a preventable disease. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives. Most countries have legislation designed to criminalize some drugs. To decrease the prevalence of this problem in our setting; increase awareness, promoting additional research on abused and addictive drugs, and exact implementation of existing laws are strongly recommended. We should

  12. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  13. Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions

    MedlinePlus

    ... Home Current Issue Past Issues Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions Past Issues / ... Drug Abuse during their first Drug Facts Chat Day. Photo courtesy of NIDA The questions poured in… ...

  14. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  15. Drugs Approved for Wilms Tumor

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Wilms tumor and other childhood kidney cancers. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  16. Drugs Approved for Kaposi Sarcoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  18. How to Read Drug Labels

    MedlinePlus

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  19. COPD - quick-relief drugs

    MedlinePlus

    COPD - quick-relief drugs; Chronic obstructive pulmonary disease - control drugs; Chronic obstructive airways disease - quick-relief drugs; Chronic obstructive lung disease - quick-relief drugs; Chronic bronchitis - quick-relief ...

  20. Drugs Approved for Skin Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.