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Sample records for pentobarbital induced hypnotic

  1. Flos Albiziae aqueous extract and its active constituent quercetin potentiate the hypnotic effect of pentobarbital via the serotonergic system

    PubMed Central

    YE, MENG-FEI; LIU, ZHENG; LOU, SHU-FANG; CHEN, ZHEN-YONG; YU, AI-YUE; LIU, CHUN-YAN; YU, CHAO-YANG; ZHANG, HUA-FANG; ZHANG, JIAN

    2015-01-01

    Flos albiziae (FA) is reportedly used for treatment of insomnia and anxiety in traditional medicine. The hypnotic effect of an extract of FA (FAE) and its constituent quercetin [2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, QR] was examined in mice. QR is a widely distributed natural flavonoid abundant in FA flowers and other tissues. The possible mechanisms underlying the hypnotic effects of FAE and QR were investigated using behavioral pharmacology. FAE and QR significantly potentiated pentobarbital-induced [50 mg/kg, intraperitoneal (ip)] sleep (prolonged sleeping time; shortened sleep latency) in a dose-dependent manner, and these effects were augmented by administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine. With a sub-hypnotic dose of pentobarbital (28 mg/kg, ip), FAE and QR significantly increased the rate of sleep onset and were synergistic with 5-HTP (2.5 mg/kg, ip). Pretreatment with p-chlorophenylalanine, an inhibitor of tryptophan hydroxylase, significantly decreased sleeping time and prolonged sleep latency in pentobarbital-treated mice, whereas FAE and QR significantly reversed this effect. Data show that FAE and QR have hypnotic activity, possibly mediated by the serotonergic system. The present study offers a rationale for the use of FA in treating sleep disorders associated with serotonin system dysfunction. PMID:26623026

  2. Hypnotically induced somatosensory alterations: Toward a neurophysiological understanding of hypnotic anaesthesia.

    PubMed

    Zeev-Wolf, Maor; Goldstein, Abraham; Bonne, Omer; Abramowitz, Eitan G

    2016-07-01

    Whereas numerous studies have investigated hypnotic analgesia, few have investigated hypnotic anaesthesia. Using magnetoencephalography (MEG) we investigated and localized brain responses (event-related fields and oscillatory activity) during sensory processing under hypnotic anaesthesia. Nineteen right handed neurotypical individuals with moderate-to-high hypnotizability received 100 vibrotactile stimuli to right and left index fingers in a random sequence. Thereafter a hypnotic state was induced, in which anaesthetic suggestion was applied to the left hand only. Once anaesthetic suggestion was achieved, a second, identical, session of vibrotactile stimuli was commenced. We found greater brain activity in response to the stimuli delivered to the left (attenuated) hand before hypnotic anaesthesia, than under hypnotic anaesthesia, in both the beta and alpha bands. In the beta band, the reduction of activity under hypnotic anaesthesia was found around 214-413ms post-stimuli and was located mainly in the right insula. In the alpha band, it was found around 253-500ms post-stimuli and was located mainly in the left inferior frontal gyrus. In a second experiment, attention modulation per se was ruled out as the underlying cause of the effects found. These findings may suggest that the brain mechanism underlying hypnotic anaesthesia involves top-down somatosensory inhibition and, therefore, a reduction of somatosensory awareness. The result of this mechanism is a mental state in which individuals lose bodily sensation. PMID:27212058

  3. Potentiation of pentobarbital hypnosis by Rosa damascena in mice.

    PubMed

    Rakhshandah, H; Hosseini, M

    2006-11-01

    Rosa damascena has been found to act on central nervous system including brain. It inhibits the reactivity of the hypothalamous and pituitary systems in rat. In traditional medicine hypnotic effect of Rose is also suggested. In the present study hypnotic effect of ethanolic, aqueous and chloroformic extracts of R. damascena was investigated in mice. Hypnotic method was based on potentiation of pentobarbital induced sleeping time by extracts. Three doses of extracts (100, 500 and 1000 mg/kg) were injected i.p. in comparison with diazepam (3mg/kg) as positive control and saline as negative control. After 30 min of injection of extracts, pentobarbital (30mg/kg) was injected and increase in sleeping time by extracts was recorded. The results showed that the ethanolic and aqueous extracts in 500 and 1000 mg/kg doses significantly increased pentobarbital induced sleeping time which was comparable to diazepam. The chloroformic extract had no hypnotic effect. PMID:17205713

  4. EXTRAPULMONARY EFFECTS OF NO2 AS REFLECTED BY PENTOBARBITAL-INDUCED SLEEPING TIME IN MICE

    EPA Science Inventory

    The influence of nitrogen dioxide (NO2) on pentobarbital(PEN)-induced sleeping time (S.T.) was investigated in mice. Acute exposure to concentrations as low as 470 micrograms NO2/cu m (0.25 ppm) caused a significant increase in PEN-induced S.T. No significant effects on PEN-induc...

  5. INCREASED SUSCEPTIBILITY TO PENTOBARBITAL FOLLOWING MOUSE CYTOMEGALOVIRUS INFECTION: ROLE OF VIRAL-INDUCED INTERFERON

    EPA Science Inventory

    The purpose of this study was to determine the relative roles of viral induced interferon (IFN) and viral infection of the liver in mouse cytomegalovirus (MCMV)-induced depression of cytochrome P-450 (cyt P-450) levels and enhancement of pentobarbital-induced sleeping time (PEN-S...

  6. Alterations in glucose kinetics induced by pentobarbital anesthesia

    SciTech Connect

    Lang, C.H.; Bagby, G.J.; Hargrove, D.M.; Hyde, P.M.; Spitzer, J.J. )

    1987-12-01

    Because pentobarbital is often used in investigations related to carbohydrate metabolism, the in vivo effect of this drug on glucose homeostasis was studied. Glucose kinetics assessed by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose, were determined in three groups of catheterized fasted rats: conscious, anesthetized and body temperature maintained, and anesthetized but body temperature not maintained. After induction of anesthesia, marked hypothermia developed in rats not provided with external heat. Anesthetized rats that developed hypothermia showed a decrease in mean arterial blood pressure (25%) and heart rate (40%). Likewise, the plasma lactate concentration and the rates of glucose appearance, recycling, and metabolic clearance were reduced by 30-50% in the hypothermic anesthetized rats. Changes in whole-body carbohydrate metabolism were prevented when body temperature was maintained. Because plasma pentobarbital levels were similar between the euthermic and hypothermic rats during the first 2 h of the experiment, the rapid reduction in glucose metabolism in this latter group appears related to the decrease in body temperature. The continuous infusion of epinephrine produced alterations in glucose kinetics that were not different between conscious animals and anesthetized rats with body temperature maintained. Thus pentobarbital-anesthetized rats became hypothermic when kept at room temperature and exhibited marked decreases in glucose metabolism. Such changes were absent when body temperature was maintained during anesthesia.

  7. Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice.

    PubMed

    Jeon, Se Jin; Park, Ho Jae; Gao, Qingtao; Pena, Irene Joy Dela; Park, Se Jin; Lee, Hyung Eun; Woo, Hyun; Kim, Hee Jin; Cheong, Jae Hoon; Hong, Eunyoung; Ryu, Jong Hoon

    2015-09-01

    Prunella vulgaris is widely used as a herbal medicine for cancers, inflammatory diseases, and other infections. Although it has long been used, few studies have examined its effects on central nervous system function. Here, we first observed that ethanolic extracts of P. vulgaris (EEPV) prolonged pentobarbital-induced sleep duration in mice. It is known that EEPV consists of many active components including triterpenoid (ursolic acid and oleanolic acid), which have many biological activities. Therefore, we evaluated which EEPV components induced sleep extension in pentobarbital-mediated sleeping model in mice. Surprisingly, despite their structural similarity and other common functions such as anti-inflammation, anti-cancer, and tissue protection, only ursolic acid enhanced sleep duration in pentobarbital-treated mice. These results were attenuated by bicuculline treatment, which is a GABAA receptor antagonist. The present results suggest that ursolic acid from P. vulgaris enhances sleep duration through GABAA receptor activation and could be a therapeutic candidate for insomnia treatment. PMID:26102564

  8. INFLUENCE OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME IN MICE, RATS, AND HAMSTERS

    EPA Science Inventory

    Prior studies have shown that ozone (O3) increases pentobarbital (PEN)-induced sleeping time (S.T.) in female mice, rats, and hamsters. To investigate some potential mechanisms producing these effects, the authors measured zoxazolamine-induced paralysis time and thiopental- and h...

  9. Pentobarbital-Induced Myocardial Stunning in Status Epilepticus Requiring Extracorporeal Membrane Oxygenation: A Case Report and Literature Review.

    PubMed

    Kavi, Tapan; Molaie, Donna; Nurok, Michael; Rosengart, Axel; Lahiri, Shouri

    2016-01-01

    Introduction. Mild hypotension is a well-recognized complication of intravenous pentobarbital; however fulminant cardiopulmonary failure has not been previously reported. Case Report. A 28-year-old woman developed pentobarbital-induced cardiopulmonary failure that was successfully treated with maximal medical management including arteriovenous extracorporeal membrane oxygenation. She made an excellent cardiopulmonary and neurological recovery. Discussion and Conclusion. Pentobarbital is underrecognized as a potential cause of myocardial stunning. The mechanism involves direct myocardial depression and inhibition of autonomic neuroanatomical structures including the medulla and hypothalamus. Early recognition and implementation of aggressive cardiopulmonary support are essential to optimize the likelihood of a favorable outcome. PMID:27529037

  10. Pentobarbital-Induced Myocardial Stunning in Status Epilepticus Requiring Extracorporeal Membrane Oxygenation: A Case Report and Literature Review

    PubMed Central

    Molaie, Donna; Nurok, Michael; Rosengart, Axel; Lahiri, Shouri

    2016-01-01

    Introduction. Mild hypotension is a well-recognized complication of intravenous pentobarbital; however fulminant cardiopulmonary failure has not been previously reported. Case Report. A 28-year-old woman developed pentobarbital-induced cardiopulmonary failure that was successfully treated with maximal medical management including arteriovenous extracorporeal membrane oxygenation. She made an excellent cardiopulmonary and neurological recovery. Discussion and Conclusion. Pentobarbital is underrecognized as a potential cause of myocardial stunning. The mechanism involves direct myocardial depression and inhibition of autonomic neuroanatomical structures including the medulla and hypothalamus. Early recognition and implementation of aggressive cardiopulmonary support are essential to optimize the likelihood of a favorable outcome. PMID:27529037

  11. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

    SciTech Connect

    Oldfield, E.H.; Friedman, R.; Kinsella, T.; Moquin, R.; Olson, J.J.; Orr, K.; DeLuca, A.M. )

    1990-05-01

    To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.

  12. Cerebral activity during the anesthesia-like state induced by mesopontine microinjection of pentobarbital.

    PubMed

    Abulafia, Ruth; Zalkind, Vladimir; Devor, Marshall

    2009-05-27

    Microinjection of pentobarbital into a restricted region of rat brainstem, the mesopontine tegmental anesthesia area (MPTA), induces a reversible anesthesia-like state characterized by loss of the righting reflex, atonia, antinociception, and loss of consciousness as assessed by electroencephalogram synchronization. We examined cerebral activity during this state using FOS expression as a marker. Animals were anesthetized for 50 min with a series of intracerebral microinjections of pentobarbital or with systemic pentobarbital and intracerebral microinjections of vehicle. FOS expression was compared with that in awake animals microinjected with vehicle. Neural activity was suppressed throughout the cortex whether anesthesia was induced by systemic or MPTA routes. Changes were less consistent subcortically. In the zona incerta and the nucleus raphe pallidus, expression was strongly suppressed during systemic anesthesia, but only mildly during MPTA-induced anesthesia. Dissociation was seen in the tuberomammillary nucleus where suppression occurred during systemic-induced anesthesia only, and in the lateral habenular nucleus where activity was markedly increased during systemic-induced anesthesia but not following intracerebral microinjection. Several subcortical nuclei previously associated with cerebral arousal were not affected. In the MPTA itself FOS expression was suppressed during systemic anesthesia. Differences in the pattern of brain activity in the two modes of anesthesia are consistent with the possibility that anesthetic endpoints might be achieved by alternative mechanisms: direct drug action for systemic anesthesia or via ascending pathways for MPTA-induced anesthesia. However, it is also possible that systemically administered agents induce anesthesia, at least in part, by a primary action in the MPTA with cortical inhibition occurring secondarily. PMID:19474332

  13. Pentobarbital overdose

    MedlinePlus

    Symptoms of a pentobarbital overdose may include: Coma Confusion Decreased energy Delirium (confusion and agitation) Difficulty breathing Headache Large blisters Rash Sleepiness Slowed or stopped breathing Slurred speech Unsteady gait

  14. Effects of olfactory stimulation with jasmin and its component chemicals on the duration of pentobarbital-induced sleep in mice.

    PubMed

    Tsuchiya, T; Tanida, M; Uenoyama, S; Nakayama, Y

    1992-01-01

    The effect of olfactory stimulation with jasmin and its component chemicals on pentobarbital sleep time was investigated using mice. In the present study we sought to determine which component of jasmin influences pentobarbital sleep time via olfactory stimulation. Sleep time was defined as the time elapsed between intraperitoneal pentobarbital administration and the first time that the animal was able to spontaneously right itself. Sleep time was significantly decreased by olfactory stimulation with jasmin, and also by one of the fractions obtained by fractional distillation at 150 degrees C and 0.1 mmHg. The fraction which influenced the sleep time was found to consist of benzyl benzoate, isophytol, geranyl linalool, phytol and phytyl acetate, which were identified using gas chromatography with mass and infrared spectrometry. In experiments using authentic samples of these components, phytol significantly shortened the pentobarbital sleep time, while the others had no effect. We conclude that phytol is the component of jasmin which reduces the duration of pentobarbital-induced sleep. PMID:1556904

  15. The influence of pilocarpine and atropine on pentobarbital-induced nystagmus in the New Zealand white rabbit.

    PubMed

    Kairys, D J; Smith, M B

    1979-12-01

    Nystagmus, induced by intravenous pentobarbital in rabbits, increased in frequency and amplitude as a result of intravenous pilocarpine administration. In seven of nine animals anesthetized with pentobarbital but not showing eye movements, pilocarpine injection elicited nystagmus. In all rabbits, nystagmus was terminated by subsequent intravenous administration of atropine, indicating that the parasympathetic nervous system contributes to nystagmus observed in barbiturate treated animals. The results reported here are of value in their implication for an understanding of the physiologic mechanisms which underlie eye movement disorders commonly observed in barbituarate intoxicated individuals. PMID:521585

  16. Hypnotic effect of the essential oil from the leaves of Myrtus communis on mice

    PubMed Central

    Birhanie, Muluken Walle; Walle, Bizuayehu; Rebba, Kidist

    2016-01-01

    Background Myrtus communis has been suggested as a sleep aid in unconventional medicine. Moreover, previous studies have also indicated its sedative- and hypnotic-like activity. In this study, the hypnotic effect of M. communis was investigated. Methods Essential oil (EO) of M. communis (600, 800, and 1,000 mg/kg) was given orally to Swiss albino mice of both sex, and the hypnotic effect was evaluated. In addition, the EO of M. communis (500, 600, 800, and 1,000 mg/kg) was administered orally to Swiss albino mice of both sex 60 minutes prior to pentobarbital injection (50 mg/kg). Latency to sleep and sleep duration were recorded. The effect of the EO on motor coordination and muscle relaxation was evaluated using chimney and traction tests, 60 and 90 minutes after administration of the respective doses of the EO, respectively. Results There was no induction of hypnosis as the presence of the righting reflex was intact. However the EO prolonged pentobarbital-induced sleeping time and there was also 50% negative response on the chimney and traction test in a dose dependent manner. Conclusion The EO of M. communis did not produce a hypnotic effect, but it potentiated a hypnotic effect with significant central nervous system depressant activity. PMID:27574478

  17. Pentobarbital-induced apneusis in intact, vagotomized, and pneumotaxic-lesioned cats.

    PubMed

    Webber, C L; Peiss, C N

    1979-09-01

    While recording several respiratory parameters, sodium pentobarbital (PB) was infused into the inferior vena cava of spontaneously breathing, PB anesthetized cats. Three cat groups were investigated: intact control (group A); vagotomized (group B); pneumotaxic center-lesioned (group C). With a few exceptions, all cats developed PB-induced inspiratory apneusis. Groups B and C exhibited 10-sec inspiratory hold pattern at significantly lower PB levels than group A cats. All groups developed apnea at different PB levels. Ventilation was consistently depressed, predominantly by breathing frequently attenuation. Tidal volume remained comparable to control, but decreased in vagotomized cats at high PB levels. These results are interpreted to signify that (1) inspiratory inhibitory inputs are more susceptible to depression by PB than inspiratory drive mechanisms; (2) the breathing pattern of apneusis results when summed inspiratory inhibition is reduced below a critical minimum level; (3) vagal and pneumotaxic center inhibitions on inspiration are equally weighted at apneusis, but not at apnea. These results are further discussed in terms of the inspiratory off-switch model. A possible model of Biot respiration is also introduced. PMID:515561

  18. Hydroalcoholic extract of needles of Pinus eldarica enhances pentobarbital-induced sleep: possible involvement of GABAergic system

    PubMed Central

    Forouzanfar, Fatemeh; Ghorbani, Ahmad; Hosseini, Mahmoud; Rakhshandeh, Hassan

    2016-01-01

    Objective: Insomnia is accompanied by several health complications and the currently used soporific drugs can induce several side effects such as psychomotor impairment, amnesia, and tolerance. The present study was planned to investigate the sleep prolonging effect of Pinus eldarica. Materials and Methods: Hydroalcoholic extract (HAE) of P. eldarica, its water fraction (WF), ethyl acetate fraction (EAF) and n-butanol fraction (NBF) were injected (intraperitoneally) to mice 30 min before administration of pentobarbital. Then, the latent period and continuous sleeping time were recorded. Also, LD50 of P. eldarica extract was determined and the possible neurotoxicity of the extract was tested on neural PC12 cells. Results: The HAE and NBF decreased the latency of sleep (p<0.05) and significantly increased duration of sleep (p<0.05) induced by pentobarbital. These effects of P. eldarica were reversed by flumazenil. The LD50 value for HAE was found to be 4.8 g/Kg. HAE and its fractions did not show neurotoxic effects in cultured PC12-cell line. Conclusion: The present data indicate that P. eldarica potentiated pentobarbital hypnosis without major toxic effect. Most probably, the main components responsible for this effect are non-polar agents which are found in NBF of this plant. PMID:27516986

  19. Tolerance to ethanol and cross-tolerance to pentobarbital and barbital in four rat strains.

    PubMed

    Khanna, J M; Kalant, H; Shah, G; Chau, A

    1991-07-01

    Chronic ethanol treatment by gastric intubation conferred tolerance to ethanol-induced motor impairment and hypnosis in four different rat strains: Fischer 344, Long-Evans, Sprague-Dawley, and Wistar. Cross-tolerance to barbital was also observed in all strains after chronic treatment with ethanol. However, chronic ethanol treatment failed to produce cross-tolerance to pentobarbital-induced motor impairment and hypnosis in any of the four strains. The demonstration of cross-tolerance to barbital and the lack of it to pentobarbital after chronic ethanol treatment confirms and extends recent observations on the specificity of the site and/or mechanism of action of sedative-hypnotic drugs that differ in lipid solubility. PMID:1784599

  20. Positive effects of β-amyrin on pentobarbital-induced sleep in mice via GABAergic neurotransmitter system.

    PubMed

    Jeon, Se Jin; Park, Ho Jae; Gao, Qingtao; Lee, Hyung Eun; Park, Se Jin; Hong, Eunyoung; Jang, Dae Sik; Shin, Chan Young; Cheong, Jae Hoon; Ryu, Jong Hoon

    2015-09-15

    Sleep loss, insomnia, is considered a sign of imbalance of physiological rhythm, which can be used as pre-clinic diagnosis of various neuropsychiatric disorders. The aim of the present study is to understand the pharmacological actions of α- or β-amyrin, natural triterpene compound, on the sleep in mice. To analyze the sleeping behavior, we used the well-known pentobarbital-induced sleeping model after single administration of either α- or β-amyrin. The sleeping onset time was remarkably decreased and duration was prolonged by β-amyrin (1, 3, or 10mg/kg) but not by α-amyrin (1, 3, or 10mg/kg). These effects were significantly blocked by GABAA receptor antagonist, bicuculline. Moreover, β-amyrin increased brain GABA level compared to the vehicle administration. Overall, the present study suggests that β-amyrin would enhance the total sleeping behavior in pentobarbital-induced sleeping model via the activation of GABAergic neurotransmitter system through GABA content in the brain. PMID:26026786

  1. Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors.

    PubMed

    Wang, L-E; Cui, X-Y; Cui, S-Y; Cao, J-X; Zhang, J; Zhang, Y-H; Zhang, Q-Y; Bai, Y-J; Zhao, Y-Y

    2010-05-01

    Previous results have suggested that spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, potentiates pentobarbital-induced sleep via the serotonergic system. The present study investigated whether spinosin potentiates pentobarbital-induced sleep via serotonin-1A (5-hydroxytryptamine, 5-HT(1A)) receptors. The results demonstrated that spinosin significantly augmented pentobarbital (35 mg/kg, i.p.)-induced sleep in rats, reflected by reduced sleep latency and increased total sleep time, non-rapid eye movement (NREM) sleep time, and REM sleep time. With regard to NREM sleep duration, spinosin mainly increased slow-wave sleep (SWS). Additionally, spinosin (15mg/kg, i.g.) significantly antagonized 5-HT(1A) agonist 8-OH-DPAT (0.1mg/kg, i.p.)-induced reductions in total sleep time, NREM sleep, REM sleep, and SWS in pentobarbital-treated rats. These results suggest that spinosin may be an antagonist at postsynaptic 5-HT(1A) receptors because these effects of 8-OH-DPAT were considered to be mediated via postsynaptic 5-HT(1A) receptors. Moreover, co-administration of spinosin and the 5-HT(1A) antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylbenzamide (p-MPPI), at doses that are ineffective when administered alone (spinosin 5mg/kg, p-MPPI 1mg/kg), had significant augmentative effects on pentobarbital-induced sleep, reflected by reduced sleep latency and increased total sleep time, NREM sleep, and REM sleep. In contrast to the attenuating effects of p-MPPI on REM sleep via presynaptic 5-HT(1A) autoreceptors, 15mg/kg spinosin significantly increased REM sleep. These results suggest that the effect of spinosin on REM sleep in pentobarbital-treated rats may be related to postsynaptic 5-HT(1A) receptors. PMID:20171860

  2. Hypoxic ventilatory drive in dogs during thiopental, ketamine, or pentobarbital anesthesia.

    PubMed

    Hirshman, C A; McCullough, R E; Cohen, P J; Weil, J V

    1975-12-01

    The ventilatory responses to isocapnic hypoxia and hypercapnia were studied in seven chronically tracheostomized dogs awake and during anesthesia with pentobarbital (30 mg/kg, iv), ketamine, or thiopental (10 and 15 mg/kg, respectively, followed by infusion). Isocapnic hypoxic ventilatory drive (HVD) was expressed as the parameter A such that the higher the A, the greater the hypoxic drive. HVD(A) was significantly reduced from 259 +/- 28 (mean +/- SEM) in awake dogs, to 96 +/- 14 after pentobarbital, 161 +/- 27 after thiopental, and 213 +/- 23 after ketamine. Hypercapnic ventilatory drive (HCVD) as measured by S (slope of the VE-PACO2 response curve) was significantly reduced from 1.3 +/- .32 in awake dogs to 0.4 +/- .13 after pentobarbital, 0.5 +/- .12 after thiopental, and 0.6 +/- .11 after ketamine. In addition, hypercapnia-induced augmentation of hypoxic drive was markedly diminished by the two barbiturates but was unaffected by ketamine. Therefore, ketamine at this dose level afforded greater protection during exposure to hypoxia than did barbiturates. (Key words: Ventilation, hypoxic response; Hypoxia, ventilation; Oxygen, ventilatory response; Carbon dioxide, ventilatory response; Anesthetics, intravenous, ketamine; Anesthetics, intravenous, thiopental; Hypnotics, barbiturates, pentobarbital.) PMID:1190538

  3. Lotus Leaf Alkaloid Extract Displays Sedative-Hypnotic and Anxiolytic Effects through GABAA Receptor.

    PubMed

    Yan, Ming-Zhu; Chang, Qi; Zhong, Yu; Xiao, Bing-Xin; Feng, Li; Cao, Fang-Rui; Pan, Rei-Le; Zhang, Ze-Sheng; Liao, Yong-Hong; Liu, Xin-Min

    2015-10-28

    Lotus leaves have been used traditionally as both food and herbal medicine in Asia. Open-field, sodium pentobarbital-induced sleeping and light/dark box tests were used to evaluate sedative-hypnotic and anxiolytic effects of the total alkaloids (TA) extracted from the herb, and the neurotransmitter levels in the brain were determined by ultrafast liquid chromatography-tandem mass spectrometry. The effects of picrotoxin, flumazenil, and bicuculline on the hypnotic activity of TA, as well as the influence of TA on Cl(-) influx in cerebellar granule cells, were also investigated. TA showed a sedative-hypnotic effect by increasing the brain level of γ-aminobutyric acid (GABA), and the hypnotic effect could be blocked by picrotoxin and bicuculline, but could not be antagonized by flumazenil. Additionally, TA could increase Cl(-) influx in cerebellar granule cells. TA at 20 mg/kg induced anxiolytic-like effects and significantly increased the concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and dopamine (DA). These data demonstrated that TA exerts sedative-hypnotic and anxiolytic effects via binding to the GABAA receptor and activating the monoaminergic system. PMID:26448283

  4. Total Phenolics and Total Flavonoids Contents and Hypnotic Effect in Mice of Ziziphus mauritiana Lam. Seed Extract

    PubMed Central

    San, Aye Moh Moh; Thongpraditchote, Suchitra; Sithisarn, Pongtip; Gritsanapan, Wandee

    2013-01-01

    The seeds of Ziziphus mauritiana Lam. have been traditionally used for treatment of various complications including insomnia and anxiety. They are popularly used as sedative and hypnotic drugs in China, Korea, Myanmar, Vietnam, and other Asian countries. However, no scientific proof on hypnotic activity of Z. mauritiana seeds (ZMS) was reported. In this study, the hypnotic activity of 50% ethanolic extract from ZMS was observed on the loss of righting reflex in mice using pentobarbital-induced sleep mice method. The contents of total phenolics and total flavonoids in the extract were also determined. The results showed that the 50% ethanolic extract from ZMS contained total phenolics 27.62 ± 1.43 mg gallic acid equivalent (GAE)/g extract and total flavonoids 0.74 ± 0.03 mg quercetin equivalent (QE)/g extract. Oral administration of the extract at the dose of 200 mg/kg significantly increased the sleeping time in mice intraperitoneally administered with sodium pentobarbital (50 mg/kg body weight). These results supported the traditional use of ZMS for the treatment of insomnia. The seeds of Z. mauritiana should be further developed as an alternative sedative and/or hypnotic product. PMID:23861716

  5. Total Phenolics and Total Flavonoids Contents and Hypnotic Effect in Mice of Ziziphus mauritiana Lam. Seed Extract.

    PubMed

    San, Aye Moh Moh; Thongpraditchote, Suchitra; Sithisarn, Pongtip; Gritsanapan, Wandee

    2013-01-01

    The seeds of Ziziphus mauritiana Lam. have been traditionally used for treatment of various complications including insomnia and anxiety. They are popularly used as sedative and hypnotic drugs in China, Korea, Myanmar, Vietnam, and other Asian countries. However, no scientific proof on hypnotic activity of Z. mauritiana seeds (ZMS) was reported. In this study, the hypnotic activity of 50% ethanolic extract from ZMS was observed on the loss of righting reflex in mice using pentobarbital-induced sleep mice method. The contents of total phenolics and total flavonoids in the extract were also determined. The results showed that the 50% ethanolic extract from ZMS contained total phenolics 27.62 ± 1.43 mg gallic acid equivalent (GAE)/g extract and total flavonoids 0.74 ± 0.03 mg quercetin equivalent (QE)/g extract. Oral administration of the extract at the dose of 200 mg/kg significantly increased the sleeping time in mice intraperitoneally administered with sodium pentobarbital (50 mg/kg body weight). These results supported the traditional use of ZMS for the treatment of insomnia. The seeds of Z. mauritiana should be further developed as an alternative sedative and/or hypnotic product. PMID:23861716

  6. Gastrodiae Rhizoma Ethanol Extract Enhances Pentobarbital-Induced Sleeping Behaviors and Rapid Eye Movement Sleep via the Activation of GABA A -ergic Transmission in Rodents.

    PubMed

    Choi, Jae Joon; Oh, Eun-Hye; Lee, Mi Kyeong; Chung, Youn Bok; Hong, Jin Tae; Oh, Ki-Wan

    2014-01-01

    This research was designed to identify whether Gastrodiae Rhizoma ethanol extract (GREE) enhances pentobarbital-induced sleep via  γ-aminobutyric acid- (GABA-) ergic systems and modulated sleep architectures in animals. GREE (25, 50, and 100 mg/kg, p.o.) inhibited locomotor activity in mice, in a dose-dependent manner. GREE not only prolonged total sleep time, but also reduced sleep latency time in pentobarbital (42 mg/kg)-treated mice. Subhypnotic pentobarbital (28 mg/kg, i.p.) also increased the number of total sleeping animals in concomitant administration of GREE. GREE (100 mg/kg) alone reduced the count of sleep-wake cycles in electroencephalogram. Furthermore, GREE increased total sleep time and rapid eye movement (REM) sleep. From the in vitro experiments, GREE increased intracellular chloride level in primary cultured cerebellar granule cells. Protein expressions of glutamine acid decarboxylase (GAD) and GABAA receptors subtypes by western blot were increased. Therefore, our study suggested that GREE enhances pentobarbital-induced sleeping behaviors and increased REM via the activation of GABAA-ergic transmission in rodents. PMID:25614750

  7. Gastrodiae Rhizoma Ethanol Extract Enhances Pentobarbital-Induced Sleeping Behaviors and Rapid Eye Movement Sleep via the Activation of GABAA-ergic Transmission in Rodents

    PubMed Central

    Choi, Jae Joon; Oh, Eun-Hye; Lee, Mi Kyeong; Chung, Youn Bok; Hong, Jin Tae; Oh, Ki-Wan

    2014-01-01

    This research was designed to identify whether Gastrodiae Rhizoma ethanol extract (GREE) enhances pentobarbital-induced sleep via  γ-aminobutyric acid- (GABA-) ergic systems and modulated sleep architectures in animals. GREE (25, 50, and 100 mg/kg, p.o.) inhibited locomotor activity in mice, in a dose-dependent manner. GREE not only prolonged total sleep time, but also reduced sleep latency time in pentobarbital (42 mg/kg)-treated mice. Subhypnotic pentobarbital (28 mg/kg, i.p.) also increased the number of total sleeping animals in concomitant administration of GREE. GREE (100 mg/kg) alone reduced the count of sleep-wake cycles in electroencephalogram. Furthermore, GREE increased total sleep time and rapid eye movement (REM) sleep. From the in vitro experiments, GREE increased intracellular chloride level in primary cultured cerebellar granule cells. Protein expressions of glutamine acid decarboxylase (GAD) and GABAA receptors subtypes by western blot were increased. Therefore, our study suggested that GREE enhances pentobarbital-induced sleeping behaviors and increased REM via the activation of GABAA-ergic transmission in rodents. PMID:25614750

  8. What Happens When You're Hypnotized?

    MedlinePlus

    ... Each was scanned while resting, when recalling a memory, and when exposed to a message intended to induce a hypnotic trance. People highly susceptible to hypnosis experienced three distinct brain changes while hypnotized that ...

  9. Anxiolytic and sedative-hypnotic activities of polygalasaponins from Polygala tenuifolia in mice.

    PubMed

    Yao, Yi; Jia, Min; Wu, Jian-Guo; Zhang, Hong; Sun, Lian-Na; Chen, Wan-Sheng; Rahman, Khalid

    2010-07-01

    In the present study, the anxiolytic and sedative-hypnotic activities of polygalasaponins extracted from Polygala tenuifolia Willdenow (Polygalaceae) were determined in mice using hole-board, elevated plus maze, open field, and sodium pentobarbital-induced hypnosis tests. Moreover, the acute toxicity of polygalasaponins was also estimated in mice. Sixty minutes after p.o. administration of polygalasaponins (40, 80, 160 mg/kg) in mice, the central crossing counts and percentage of central/total ambulation significantly increased and the number of rearings and defecations was evidently inhibited in the open field test. Polygalasaponins also increased the head-dips of mice in the hole-board test and the time spent by mice in the open arms of the X-maze, prolonged sleep duration and shortened sleep latency in the test of synergetic effect on sodium pentobarbital (45 and 25 mg/kg, respectively). Acute toxic study showed the oral median lethal dose (LD(50)) of polygalasaponins was 3.95 g/kg and 0% lethal dose 2.6 g/kg. These results suggest that polygalasaponin possesses evident anxiolytic and sedative-hypnotic activities and has a relatively safe dose range, which supports the use of Polygala tenuifolia root as an anxiolytic and sedative-hypnotic drug in folk medicine. PMID:20645780

  10. Anxiolytic and Hypnotic Effects of Aqueous and Ethanolic Extracts of Aerial Parts of Echium italicum L. in Mice

    PubMed Central

    Hosseinzadeh, Hossein; Shahandeh, Shabnam; Shahsavand, Shabnam

    2012-01-01

    Background Research in the area of herbal psychopharmacology has clearly improved in recent decades. Self-administration of herbal medicines has been the most popular therapeutic alternative to standard medicine. Objectives Since the extract of Echium amoenum exhibits an anxiolytic effect, the aim of this study is to evaluate the anxiolytic and hypnotic effects in mice of the aqueous and ethanolic extracts of aerial parts of E. italicum, a member of the Boraginaceae family. Materials and Methods Mice were administered the agents intraperitoneally before the start of the experiments for evaluation of hypnotic activity (induced by sodium pentobarbital, 30 mg/kg, i.p.), anxiolytic activity (elevated plus-maze [EPM] test), locomotor activity (open field test), and motor coordination (rotarod test). Result The ethanolic and aqueous extracts of E. italicum, at doses of 1.2 and 2.1 g/kg, increased the percentage of time-spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time-spent in the closed arms of the EPM. Moreover, both extracts decreased the pentobarbital-induced latency to sleep and significantly increased the total sleeping time induced by pentobarbital. In addition, locomotor activity was affected by aqueous extracts and ethanolic extract (at higher doses). Both extracts showed no effect in the rotarod test. Conclusions These results suggest that both ethanolic and aqueous extracts of E. italicum may have anxiolytic effects and sedative activity but no effect on muscle relaxation. PMID:24624158

  11. [Morphological studies in different avian species on artefacts induced by euthanasia with T 61 " or Pentobarbital (Narcoren)].

    PubMed

    Kummerfeld, Norbert; Legler, Marko; Wohlsein, Peter; Kummerfeld, Maren

    2012-01-01

    In mammals (e. g. macaques, dogs, cats, rats, sheep) as well as in men (suicides) euthanasia performed by intravenous injection of T 61 leads to serious lesions in lung, kidney or/and liver (endothelial damage, hyperemia, oedema, necrosis). This is caused by the solvent dimethylformamide (DMF). In this study, in contrast, in different species of birds (e. g. blackbird, carrion crow, kestrel, common buzzard, homer pigeon, common wood pigeon, mallard duck) and various modes of applications and dosages T 61, 1.0-3.0 ml/kg body mass, did not induce comparable artefacts in tissues of internal organs in the narcotized animals. Microscopically, only hyperemia and oedema of lung, kidney and/or liver were found. However, milder but similar lesions were detected also in groups of birds euthanized by pentobarbital (200 mg/kg body mass) as well as in control groups (overdosed ketamine intramusculary, 100 mg/kg body mass, and rapid exsanguination). In conclusion, euthanasia of narcotized birds performed by intravenous or intracardial injections ofT 61 seemed to be suitable. The observed lesions could therefore not be interpreted as T61 induced artefacts. PMID:22372321

  12. Influence of ozone on pentobarbital pharmacokinetics in mice

    SciTech Connect

    Graham, J.A.; Menzel, D.B.; Mole, M.L.; Miller, F.J.; Gardner, D.E.

    1985-01-01

    It had been shown that 3- to 5-hr exposures to ambient concentrations of ozone (O/sub 3/) increase pentobarbital-induced sleeping time in female mice, hamsters, and rats without decreasing heptatic cytochrome P-450 levels or selected mixed function oxidases. To elucidate potential mechanisms involved, clearance of pentobarbital from the blood of O/sub 3/-exposed mice was examined. Pentobarbital clearance followed first-order kinetics with a one-compartment model. Mice exposed to 1960 micrograms per cu. m. (1ppm) for 5 hr had a 71% increase in the plasma half-life of pentobarbital. It therefore appears possible that pentobarbital-induced sleeping time is increased due to a decrease in hepatic metabolism of pentobarbital.

  13. Sedative-Hypnotic and Receptor Binding Studies of Fermented Marine Organisms.

    PubMed

    Joung, Hye-Young; Kang, Young Mi; Lee, Bae-Jin; Chung, Sun Yong; Kim, Kyung-Soo; Shim, Insop

    2015-09-01

    This study was performed to investigate the sedative-hypnotic activity of γ-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the GABAA-benzodiazepine and 5-HT2C receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In GABAA and 5-HT2C receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABAA receptor, similar to the binding affinity to 5-HT2C receptor. FO exhibited higher affinity to 5-HT2C receptor, compared with the GABAA receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedative-hypnotic activity possibly by modulating GABAA and 5-HT2C receptors. We propose that FST and FO might be effective agents for treatment of insomnia. PMID:26336589

  14. Sedative-Hypnotic and Receptor Binding Studies of Fermented Marine Organisms

    PubMed Central

    Joung, Hye-Young; Kang, Young Mi; Lee, Bae-Jin; Chung, Sun Yong; Kim, Kyung-Soo; Shim, Insop

    2015-01-01

    This study was performed to investigate the sedative-hypnotic activity of γ-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the GABAA-benzodiazepine and 5-HT2C receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In GABAA and 5-HT2C receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABAA receptor, similar to the binding affinity to 5-HT2C receptor. FO exhibited higher affinity to 5-HT2C receptor, compared with the GABAA receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedative-hypnotic activity possibly by modulating GABAA and 5-HT2C receptors. We propose that FST and FO might be effective agents for treatment of insomnia. PMID:26336589

  15. Hormonal responses to exercise after partial sleep deprivation and after a hypnotic drug-induced sleep.

    PubMed

    Mougin, F; Bourdin, H; Simon-Rigaud, M L; Nguyen, N U; Kantelip, J P; Davenne, D

    2001-02-01

    The aim of this study was to determine the hormonal responses, which are dependent on the sleep wake cycle, to strenuous physical exercise. Exercise was performed after different nocturnal regimens: (i) a baseline night preceded by a habituation night; (ii) two nights of partial sleep deprivation caused by a delayed bedtime or by an early awakening; and (iii) two nights of sleep after administration of either a hypnotic compound (10 mg zolpidem) or a placebo. Eight well-trained male endurance athletes with a maximal oxygen uptake of 63.5 +/- 3.8 ml x kg(-1) x min(-1) (mean value +/- s(x)) were selected on the basis of their sleeping habits and their physical training. Polygraphic recordings of EEG showed that both nights with partial sleep loss led to a decrease (P< 0.01) in stage 2 and rapid eye movement sleep. A delayed bedtime also led to a decrease (P < 0.05) in stage 1 sleep. Zolpidem had no effect on the different stages of sleep. During the afternoon after an experimental night, exercise was performed on a cycle ergometer. After a 10-min warm-up, the participants performed 30 min steady-state cycling at 75% VO(2-max) followed by a progressively increased workload until exhaustion. The recovery period lasted 30 min. Plasma growth hormone, prolactin, cortisol, catecholamine and lactate concentrations were measured at rest, during exercise and after recovery. The concentration of plasma growth hormone and catecholamine were not affected by partial sleep deprivation, whereas that of plasma prolactin was higher (P < 0.05) during the trial after an early awakening. Plasma cortisol was lower (P < 0.05) during recovery after both sleep deprivation conditions. Blood lactate was higher (P < 0.05) during submaximal exercise performed after both a delayed bedtime and an early awakening. Zolpidem-induced sleep did not affect the hormonal and metabolic responses to subsequent exercise. Our results demonstrate only minor alterations in the hormonal responses to exercise

  16. Prevention of benznidazole-induced prolonging effect on the pentobarbital sleeping time of rats using different thiol-containing compounds.

    PubMed

    Montalto de Mecca, M; Bernacchi, A S; Castro, J A

    2000-01-01

    Benznidazole (BZ) is a nitroimidazolic chemotherapeutic agent employed against the acute and indeterminate phase of Chagas' disease, a tropical sickness afflicting more than twenty million people in Latin America. BZ has serious toxic side effects forcing people to stop treatment. These effects were attributed to the nitroreductive metabolic activation of BZ to a hydronitroxide radical or the hydroxylamine, which would covalently bind to cellular components. One of these deleterious effects is the prolongation on the pentobarbital sleeping time of rats. This results from the covalent binding of BZ reactive metabolites, arisen during its nitroreductive metabolism, to the phospholipid component of the mixed function oxidase which biotransform the barbiturate. In this study, the potential ability of different thiol containing drugs to trap BZ reactive metabolites and to prevent BZ effect on the pentobarbital sleeping time was tested. Our HPLC studies evidenced that cysteine, N-acetylcysteine, penicillamine and glutathione were able to trap BZ reactive metabolites in vitro to produce one or two adducts. Reduced lipoic acid instead, decreased the intensity of the nitroreductive process without leading to detectable adducts. The in vivo administration of the thiol drugs, at dosage regimes available in literature, was able to markedly prevent the BZ prolongation effect on the sleeping time. Whether these thiols might prevent other BZ toxic effects without harming its chemotherapeutic actions remains to be established. PMID:11758973

  17. Role of effective composition on antioxidant, anti-inflammatory, sedative-hypnotic capacities of 6 common edible Lilium varieties.

    PubMed

    Wang, Tingting; Huang, Hanhan; Zhang, Yao; Li, Xia; Li, Hongfa; Jiang, Qianqian; Gao, Wenyuan

    2015-04-01

    Nine Lilium samples (belong to 6 different cultivars with different maturity stage) were qualitatively and quantitatively analyzed of total phenolics (TP), total flavonoids (TF), total saponins (TS), total carbohydrates (TC, polysaccharides), and soluble proteins contents (SP), and the monomeric components were quantified utilizing high-performance liquid chromatography with photodiode array detector (HPLC-PAD) associated with liquid chromatography-mass spectrometry (HPLC-MS). Antioxidant activity (reducing power and DPPH radical scavenging activity), anti-inflammatory (xylene-induced mouse ear edema detumescent assay and carrageenan-induced mouse paw edema detumescent assay), and sedative-hypnotic capacities (sodium pentobarbital-induced sleep assay) were comparatively evaluated in mouse model. Additionally, correlation analysis and principal component analysis were carried out to detect clustering and elucidate relationships between components' concentrations and bioactivities to clarify the role of effective composition. Lilium bulbs in later maturity stage preliminary evidenced higher saponins content, and lower phenolic acids and flavonoids content. The result demonstrated that Lilium bulbs generally had distinct antioxidant, anti-inflammatory, and sedative-hypnotic capacities. Varieties statistically differed (P < 0.05) in chemical composition and bioactivities. Lilium varieties of Dongbei and Lanzhou presented potent sedative-hypnotic effect and anti-inflammatory activity. The antioxidant capacity was related to the phenolic acids and flavonoids contents, the anti-inflammatory and sedative-hypnotic capacities were related to the saponins content. This is first study presenting comprehensive description of common edible Lilium bulbs' chemical compositions, sedative-hypnotic, and anti-inflammatory capacities grown in China. It would informatively benefit the genetic selection and cultivated optimization of Lilium varieties to improve nutritional quality, and

  18. A tryptic hydrolysate from bovine milk αs1-casein enhances pentobarbital-induced sleep in mice via the GABAA receptor.

    PubMed

    Dela Peña, Irene Joy I; Kim, Hee Jin; de la Peña, June Bryan; Kim, Mikyung; Botanas, Chrislean Jun; You, Kyung Yi; Woo, Taeseon; Lee, Yong Soo; Jung, Jae-Chul; Kim, Kyung-Mi; Cheong, Jae Hoon

    2016-10-15

    Studies have shown that enzymatic hydrolysis of casein, the primary protein component of cow's milk, produces peptides with various biological activities, and some of these peptides may have sleep-promoting effects. In the present study, we evaluated the sedative and sleep-promoting effects of bovine αS1-casein tryptic hydrolysate (CH), containing a decapeptide αS1-casein known as alpha-casozepine. CH was orally administered to ICR mice at various concentrations (75, 150, 300, or 500mg/kg). An hour after administration, assessment of its sedative (open-field and rota-rod tests) and sleep-potentiating effects (pentobarbital-induced sleeping test and EEG monitoring) were conducted. Although a trend can be observed, CH treatment did not significantly alter the spontaneous locomotor activity and motor function of mice in the open-field and rota-rod tests. On the other hand, CH (150mg/kg, respectively) enhanced the sleep induced by pentobarbital sodium in mice. It also promoted slow-wave (delta) EEG activity in rats; a pattern indicative of sleep or relaxation. These behavioral results indicate that CH has sleep-promoting effects, but no or has minimal sedative effects. To elucidate the probable mechanism behind the effects of CH, we examined its action on intracellular chloride ion influx in cultured human neuroblastoma cells. CH dose-dependently increased chloride ion influx, which was blocked by co-administration of bicuculline, a competitive GABAA receptor antagonist. Taken together, the results of the present study suggest that CH has sleep-promoting properties which are probably mediated through the GABAA receptor-chloride ion channel complex. PMID:27401107

  19. Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats.

    PubMed

    Hirase, Masahiro; Ishida, Takayuki; Kamei, Chiaki

    2008-11-12

    The present study was performed to examine whether or not rebound insomnia is caused by an abrupt withdrawal of benzodiazepine hypnotics and tandospirone in rats. Etizolam and triazolam caused a significant shortening of sleep latency, increase in non-REM sleep time, and decrease in wake time in a dose-dependent manner. Etizolam and triazolam caused a significant shortening of sleep latency during drug administration (for 7 days), whereas a significant prolongation of sleep latency was observed by the abrupt withdrawal of these drugs. Tandospirone caused a shortening of sleep latency, whereas no effect was observed on non-REM sleep time and wake time during drug administration (for 7 days). On the other hand, tandospirone showed no significant effect on sleep latency through its abrupt withdrawal, differing from etizolam and triazolam. From these findings, a rebound phenomenon in terms of sleep latency was confirmed with etizolam and triazolam in rats. Furthermore, the 5-HT(1A) agonist, tandospirone, caused no rebound phenomenon regarding sleep latency in rats. PMID:18789918

  20. Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn Neurons by Pentobarbital.

    PubMed

    Ma, Dongliang; Yoon, Su-In; Yang, Chih-Hao; Marcy, Guillaume; Zhao, Na; Leong, Wan-Ying; Ganapathy, Vinu; Han, Ju; Van Dongen, Antonius M J; Hsu, Kuei-Sen; Ming, Guo-Li; Augustine, George J; Goh, Eyleen L K

    2015-04-01

    Rett syndrome is a neurodevelopmental disorder that usually arises from mutations or deletions in methyl-CpG binding protein 2 (MeCP2), a transcriptional regulator that affects neuronal development and maturation without causing cell loss. Here, we show that silencing of MeCP2 decreased neurite arborization and synaptogenesis in cultured hippocampal neurons from rat fetal brains. These structural defects were associated with alterations in synaptic transmission and neural network activity. Similar retardation of dendritic growth was also observed in MeCP2-deficient newborn granule cells in the dentate gyrus of adult mouse brains in vivo, demonstrating direct and cell-autonomous effects on individual neurons. These defects, caused by MeCP2 deficiency, were reversed by treatment with the US Food and Drug Administration-approved drug, pentobarbital, in vitro and in vivo, possibly caused by modulation of γ-aminobutyric acid signaling. The results indicate that drugs modulating γ-aminobutyric acid signaling are potential therapeutics for Rett syndrome. PMID:25753729

  1. Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations.

    PubMed

    Fang, X Sh; Hao, J F; Zhou, H Y; Zhu, L X; Wang, J H; Song, F Q

    2010-01-01

    Semen Ziziphi spinosae (Suanzaoren in China) and Radix et Rhizoma Salviae miltiorrhizae (Danshen in China) are conventional herbal drugs in traditional Chinese medicine and have been used widely for the treatment of insomnia. In the present study, the sedative-hypnotic activity of the active fractions extracted from Suanzaoren and Danshen were studied using the method of pentobarbital-induced sleep in the mouse model. Qualitative analysis of the standardized extracts was carried out by HPLC-DAD. The results showed that the water extract of Suanzaoren (SWE) (400 and 800 mg/kg body wt.) and the ether extract of Danshen (DTT) (300 and 600 mg/kg body wt.) can shorten sleep latency significantly, increase sleeping time and prolong movement convalescence time induced by sodium pentobarbital (55 mg/kg body wt.) administration in mice. Furthermore, the combination of SWE and DTT showed significant synergistic effect (p<0.05) in decreasing sleep latency and increasing sleeping time, but not in prolonging the movement convalescence time, which might be helpful for energy recovery in the treatment of insomnia. The results suggest that SWE, DTT, and the combination of SWE and DTT possess significant sedative-hypnotic activity, which supports the popular use of Suanzaoren and Danshen for treatment of insomnia and provide the basis for new drug discovery. Furthermore, the results demonstrate that the combination of SWE and DTT may be preferable for the treatment of insomnia. PMID:19682877

  2. Potentiation of morphine analgesia by subanesthetic doses of pentobarbital.

    PubMed

    Pontani, R B; Vadlamani, N L; Misra, A L

    1985-03-01

    Pentobarbital pretreatment reportedly either inhibits, enhances or has no effect on morphine analgesia. The effect of subanesthetic doses of sodium pentobarbital (8-12 mg kg-1, SC) delivered via a delivery system on analgesia of morphine (5 mg kg-1, SC or 1 mg kg-1, IV) acutely administered 45 min after the sodium pentobarbital pellet implantation was assessed using the warm water (55 degrees C)-induced tail-withdrawal reflex in male Wistar rats. Significant potentiation of morphine analgesia was observed in sodium pentobarbital as compared to the placebo-pelleted animals. Pharmacokinetic or dispositional factors were not involved in this potentiation, which was possibly due to the activation of the descending inhibitory control pathways of nociceptive spinal tail-withdrawal reflex by a combined interaction of two drugs at spinal and supraspinal sites of action, that mediate opiate antinociception. PMID:3991755

  3. Mortality Risk of Hypnotics: Strengths and Limits of Evidence.

    PubMed

    Kripke, Daniel F

    2016-02-01

    Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p < 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival. PMID:26563222

  4. Interactions of cocaine with barbital, pentobarbital and ethanol.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1989-01-01

    This study deals with the interactions of cocaine with barbital, pentobarbital and ethanol in nontolerant and tolerant male Sprague-Dawley rats. Cocaine hydrochloride (50 mg) pellets implanted s.c. in rats prior to the i.p. injections of sodium barbital (150 mg/kg dose once daily for 4 days) potentiated the hypothermic response 2 hr after the barbital injection, when maximum hypothermia occurred. The s.c. implantation of the same type of pellets prior to the i.p. injections of sodium pentobarbital (75 mg/kg dose once daily for 5 days) potentiated the pentobarbital hypnosis as measured by the duration of loss of the righting reflex in animals. Cocaine pellets (12.5 mg) implanted s.c. in rats potentiated the hypnosis induced by ethanol (3.2 g/kg i.p.) and the implantation of the same type of pellets (12.5, 25 mg) in ethanol-tolerant rats restored the ethanol hypnosis to levels observed in acutely treated animals. The course of tolerance development to barbital-induced hypothermia or pentobarbital hypnosis did not appear to be affected by cocaine. The possible role of central monoamines in the potentiation of barbital hypothermia and pentobarbital and ethanol hypnosis by cocaine is discussed. PMID:2774771

  5. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects.

    PubMed

    Bonaventure, Pascal; Yun, Sujin; Johnson, Philip L; Shekhar, Anantha; Fitz, Stephanie D; Shireman, Brock T; Lebold, Terry P; Nepomuceno, Diane; Lord, Brian; Wennerholm, Michelle; Shelton, Jonathan; Carruthers, Nicholas; Lovenberg, Timothy; Dugovic, Christine

    2015-03-01

    Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate-induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states. PMID:25583879

  6. A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

    PubMed Central

    Yun, Sujin; Johnson, Philip L.; Shekhar, Anantha; Fitz, Stephanie D.; Shireman, Brock T.; Lebold, Terry P.; Nepomuceno, Diane; Lord, Brian; Wennerholm, Michelle; Shelton, Jonathan; Carruthers, Nicholas; Lovenberg, Timothy; Dugovic, Christine

    2015-01-01

    Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate–induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states. PMID:25583879

  7. [Benzodiazepine and nonbenzodiazepine hypnotics].

    PubMed

    Nakamura, Masaki; Inoue, Yuichi

    2015-06-01

    The prevalence of insomnia shows an age-associated increase. Especially, persons with age over 60 years frequently suffer from arousal during sleep and early-morning awakening. The reason of this phenomenon can be explained by age-related change in sleepwake regulation, comorbid diseases and psycho-social status. Benzodiazepine derivatives and benzodiazepine agonists have been widely used for treatment of insomnia. These GABA-A receptor agonist hypnotics have sedative effect, possibly causing various adverse events, i.e. falls and hip fracture, anterograde amnesia, next morning hangover especially in the elderly. When making a choice of treatment drugs for the elderly, low dose benzodiazepine hypnotics with relatively high Ω1-selectivity, and newer hypnotics including melatonic receptor agonist or orexin receptor antagonist can become important candidates considering their comorbid diseases or drug interaction with other medications. PMID:26065134

  8. INFLUENCE OF OZONE ON PENTOBARBITAL PHARMACOKINETICS IN MICE

    EPA Science Inventory

    It had been shown that 3 to 5 hr exposures to ambient concentrations of ozone (O3) increase pentobarbital-induced sleeping time in female mice, hamsters, and rats without decreasing heptatic cytochrome P-450 levels or selected mixed function oxidases. To elucidate potential mecha...

  9. Investigation of sedative and hypnotic effects of Amygdalus communis L. extract: behavioral assessments and EEG studies on rat.

    PubMed

    Abdollahnejad, Fatemeh; Mosaddegh, Mahmoud; Kamalinejad, Mohammad; Mirnajafi-Zadeh, Javad; Najafi, Forough; Faizi, Mehrdad

    2016-04-01

    Amygdalus communis L. (almond) has been traditionally used as a natural medicine in the treatment of various diseases. The present research studied the sedative and hypnotic effects of the aqueous fraction of seeds of almond in rats. In order to investigate these effects, a combination of behavioral methods (open field test and loss of righting reflex test) as well as quantitative and analytic methods (EEG and EMG) were applied. The results of the open field test showed that a dose of 400 mg/kg of the almond extract significantly inhibited the locomotion activity of rats compared to normal. The results also illustrated that the almond extract affected pentobarbital-induced sleep through increasing the number of fallings asleep and prolongation of sleeping time. Analysis of EEG recordings of the animals which had received the same dose of the almond extract as the open field test demonstrated marked changes in the animals' sleep architecture. Significant prolongation of total sleeping time as well as significant increase in NREM sleep were the main observed changes compared to the normal condition. These results suggest that the aqueous extract of almond has significant sedative and hypnotic effects, which may support its therapeutic use for insomnia. PMID:26711831

  10. Furnishing hypnotic instructions with implementation intentions enhances hypnotic responsiveness.

    PubMed

    Schweiger Gallo, Inge; Pfau, Florian; Gollwitzer, Peter M

    2012-06-01

    Forming implementation intentions has been consistently shown to be a powerful self-regulatory strategy. As the self-regulation of thoughts is important for the experience of involuntariness in the hypnotic context, investigating the effectiveness of implementation intentions on the suppression of thoughts was the focus of the present study. Participants were randomly assigned to one of four conditions (hypnotic instruction plus implementation intention, hypnotic instruction, implementation intention, and control condition). Results showed that participants who received information included in the "Carleton Skill Training Program" and in addition formed implementation intentions improved their hypnotic responsiveness as compared to all of the other three groups on measures of objective responding and involuntary responding. Thus, in line with the nonstate or cognitive social-psychological view of hypnosis stating that an individual's hypnotic suggestibility is not dispositional but modifiable, our results suggest that hypnotic responsiveness can be heightened by furnishing hypnotic instructions with ad hoc implementation intentions. PMID:22487594

  11. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    SciTech Connect

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. )

    1990-05-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.

  12. The comparative study of intravenous Ondansetron and sub-hypnotic Propofol dose in control and treatment of intrathecal Sufentanil-induced pruritus in elective caesarean surgery

    PubMed Central

    Hirmanpour, Anahita; Safavi, Mohammadreza; Honarmand, Azim; Hosseini, Akram Zavaran; Sepehrian, Maryam

    2015-01-01

    Objective: Pruritus is a common and disturbing side effect of neuraxial opioids after cesarean section. The purpose of this study was to compare the efficacy of intravenous ondansetron and sub-hypnotic dose of propofol in control and treatment of intrathecal sufentanil induced pruritus in cesarean surgery. Methods: Totally, 90 parturient with American Society of Anesthesiology physical status grade I-II, undergoing spinal anesthesia with 2.5 μg sufentanil and 10 mg bupivacaine 0.5% were enrolled to this randomized, prospective, double-blind study. The women were randomly assigned to two groups who received 8 mg ondansetron or 10 mg propofol to treat pruritus grade ≥3. The patient was evaluated after 5 min and in the lack of successful treatment, the doses of two drugs repeated and if the pruritus is on-going, the exact treatment with naloxone was done. Findings: The incidence of pruritus was 69.3%. Both groups were well-matched. The peak time pruritus was 30–75 min after injection. The percentage of individuals consumed naloxone were 6.8% and 15.9% in ondansetron and propofol groups, respectively (P = 0.18). The mean score of satisfaction (according to visual analog scale criteria) was 9.09 ± 1.1 in ondansetron group and 9.3 ± 1.07 in the propofol group (P = 0.39). Conclusion: Ondansetrone and sub-hypnotic dose of propofol are both safe and well-tolerated. Due to their same efficacy in the treatment of intrathecal sufentanil-induced pruritus, they can be widely used in clinical practice. PMID:25984542

  13. Clobazam--a new hypnotic?

    PubMed Central

    Kesson, C M; Gray, J M; Lawson, D H

    1978-01-01

    1 A double-blind randomized trial to compare the relative efficacy of the 1,5-benzodiazepine, clobazam, the 1,4-benzodiazepine nitrazepam, and placebo as hypnotics was carried out. 2 A preference technique was used and the analyses were performed sequentially. 3. The results confirmed that nitrazepam was superior to placebo as a hypnotic but failed to show that clobazam was superior to either placebo or nitrazepam in a ratio of 2:1. Thus, it seems likely that the hypnotic properties of clobazam are minimal. 4 Clobazam is not suitable for use as a hypnotic in hospitalized patients. PMID:687502

  14. Effect of chronic pentobarbital treatment on the development of cross-tolerance to ethanol and barbital.

    PubMed

    Khanna, J M; Lê, A D; Gougos, A; Kalant, H

    1988-09-01

    Recently, we reported that a chronic regimen of ethanol by intubation, which produced clear tolerance to ethanol-induced hypothermia, ataxia and sleep, produced only a marginal degree of cross-tolerance to these effects of pentobarbital. The present experiments were designed to test the reverse process by examining cross-tolerance to pentobarbital after chronic pretreatment with ethanol, chronic pentobarbital treatment by gavage conferred clear cross-tolerance to both barbital- and ethanol-induced hypothermia, ataxia and sleep. In a separate experiment, cross-tolerance to barbital- and ethanol-induced hypothermia and ataxia was demonstrated over a wide range of test doses. Determination of ethanol blood levels as well as a complete time course of absorption, distribution and elimination of ethanol suggested that pharmacokinetic alterations may play a role in the development of cross-tolerance to ethanol in pentobarbital-treated subjects. The asymmetry of cross-tolerance raises the possibility that pentobarbital and ethanol invoke tolerance by mechanisms that are not wholly identical. This possibility requires further exploration. Conceivably the actions of ethanol which mediate the measured effects form a subset of a larger range of pentobarbital actions that could provide a stronger stimulus to tolerance development. PMID:3252249

  15. Hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis extracts in mice.

    PubMed

    Hajhashemi, Valiollah; Safaei, Azadeh

    2015-01-01

    The aim of the present study was to evaluate hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis hydroalcoholic extracts in mice to select the most effective ones for a combination formula. Three doses of the extracts (250, 500 and 1000 mg/kg of C. sativum and Z. jujuba and 200, 400 and 800 mg/kg of L. angustifolia and M. officinalis) were orally administered to male Swiss mice (20-25 g) and one hour later pentobarbital (50 mg/kg, i.p.) was injected to induce sleep. Onset of sleep and its duration were measured and compared. Control animals and reference group received vehicle (10 ml/kg, p.o.) and diazepam (3 mg/kg, i.p.), respectively. C. sativum and Z. jujuba failed to change sleep parameters. L. angustifolia at doses of 200, 400 and 800 mg/kg shortened sleep onset by 7.6%, 50% and 51.5% and prolonged sleep duration by 9.9%, 43.1% and 80.2%, respectively. Compared with control group the same doses of M. officinalis also decreased sleep onset by 24.7%, 27.5% and 51.2% and prolonged sleep duration by 37.9%, 68.7% and 131.7% respectively. Combinations of L. angustifolia and M. officinalis extracts showed additive effect and it is suggested that a preparation containing both extracts may be useful for insomnia. PMID:26779267

  16. Hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis extracts in mice

    PubMed Central

    Hajhashemi, Valiollah; Safaei, Azadeh

    2015-01-01

    The aim of the present study was to evaluate hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis hydroalcoholic extracts in mice to select the most effective ones for a combination formula. Three doses of the extracts (250, 500 and 1000 mg/kg of C. sativum and Z. jujuba and 200, 400 and 800 mg/kg of L. angustifolia and M. officinalis) were orally administered to male Swiss mice (20-25 g) and one hour later pentobarbital (50 mg/kg, i.p.) was injected to induce sleep. Onset of sleep and its duration were measured and compared. Control animals and reference group received vehicle (10 ml/kg, p.o.) and diazepam (3 mg/kg, i.p.), respectively. C. sativum and Z. jujuba failed to change sleep parameters. L. angustifolia at doses of 200, 400 and 800 mg/kg shortened sleep onset by 7.6%, 50% and 51.5% and prolonged sleep duration by 9.9%, 43.1% and 80.2%, respectively. Compared with control group the same doses of M. officinalis also decreased sleep onset by 24.7%, 27.5% and 51.2% and prolonged sleep duration by 37.9%, 68.7% and 131.7% respectively. Combinations of L. angustifolia and M. officinalis extracts showed additive effect and it is suggested that a preparation containing both extracts may be useful for insomnia. PMID:26779267

  17. 21 CFR 522.1704 - Sodium pentobarbital injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium pentobarbital injection. 522.1704 Section... § 522.1704 Sodium pentobarbital injection. (a)(1) Specifications. Sodium pentobarbital injection is sterile and contains in each milliliter 64.8 milligrams of sodium pentobarbital. (2) Sponsor. See...

  18. 21 CFR 522.1704 - Sodium pentobarbital injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium pentobarbital injection. 522.1704 Section... § 522.1704 Sodium pentobarbital injection. (a)(1) Specifications. Sodium pentobarbital injection is sterile and contains in each milliliter 64.8 milligrams of sodium pentobarbital. (2) Sponsor. See...

  19. Pentobarbital anesthesia modifies pulmonary vasoregulation after hypoperfusion.

    PubMed

    Chen, B B; Nyhan, D P; Goll, H M; Clougherty, P W; Fehr, D M; Murray, P A

    1988-09-01

    Our objectives were 1) to investigate the extent to which the pulmonary vascular response to increasing cardiac index after a period of hypotension and hypoperfusion (defined as reperfusion) measured in conscious dogs is altered during pentobarbital sodium anesthesia, and 2) to determine whether pentobarbital anesthesia modifies autonomic nervous system (ANS) regulation of the pulmonary circulation during reperfusion. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise inflation and deflation, respectively, of an inferior vena caval occluder to vary Q in conscious and pentobarbital-anesthetized (30 mg/kg iv) dogs. During pentobarbital anesthesia, controlled ventilation (without positive end-expiratory pressure) allowed matching of systemic arterial and mixed venous blood gases to conscious values. Marked pulmonary vasoconstriction (P less than 0.01) was observed during reperfusion in pentobarbital-anesthetized but not in conscious dogs. Both sympathetic alpha-adrenergic receptor block and total ANS ganglionic block attenuated, but did not abolish, the pulmonary vasoconstriction during reperfusion in pentobarbital-anesthetized dogs. Neither sympathetic beta-adrenergic receptor block nor cholinergic receptor block enhanced the magnitude of the pulmonary vasoconstrictor response to reperfusion during pentobarbital anesthesia. Thus, in contrast to the conscious state, the pulmonary vascular response to reperfusion is characterized by active, non-flow-dependent pulmonary vasoconstriction during pentobarbital anesthesia. This response is primarily, but not exclusively, mediated by sympathetic alpha-adrenergic vasoconstriction and is not offset by either sympathetic beta-adrenergic or cholinergic vasodilation. These results indicate, that, compared with the conscious state, pentobarbital anesthesia modifies pulmonary vasoregulation, during reperfusion following hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250

  20. Classroom Seating and Hypnotic Susceptibility.

    ERIC Educational Resources Information Center

    Sackeim, Harold A.; And Others

    1979-01-01

    The purpose of this study was to examine whether people who differ in behavioral and self-report measures of lateralized seating preferences also differ in hypnotic susceptibility. Only right-handed subjects were used, and the associations between hypnotic susceptibility and seating preference were examined separately for males and females.…

  1. Hypnotics and Sedatives

    NASA Astrophysics Data System (ADS)

    Kabra, Pokar M.; Koo, Howard Y.; Marton, Laurence J.

    In recent years, most large hospitals have observed a marked increase in the admission of patients suffering from drug overdose. Overdose of narcotic drugs, such as the opiates, represent less of a problem on a day-to-day basis than do overdoses of prescribed drugs, such as sedatives and hypnotics. Clinical signs and symptoms for a narcotic drug overdose are very distinct, and in the majority of cases can be easily recognized by the attending physicians without the help of a toxicology laboratory. Loomis (1) reported that the majority of fatal poisonings owed to one, or a combination, of four agents: barbiturates, carbon monoxide, ethyl alcohol, and salicylates. Berry (2) estimated that 5-5'-disubstituted barbiturates were the second commonest cause of fatal poisoning in England, and that the frequency of their use was increasing. Other nonbarbiturate hypnotics involved in coma-producing incidents include glutethimide (Doriden®), methyprylon (Noludar®), and meprobamate (3, 4). In the last five years, diazepam (Valium®) has become one of the leading misused drugs (5).

  2. Marijuana Usage and Hypnotic Susceptibility

    ERIC Educational Resources Information Center

    Franzini, Louis R.; McDonald, Roy D.

    1973-01-01

    Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

  3. Hypnotic Psychotherapy with Sex Offenders

    ERIC Educational Resources Information Center

    Moseley, Sullivan; Briggs, Wanda P.; Magnus, Virginia

    2005-01-01

    The authors review the literature on the prevalence of sex offenders; multiple treatment modalities; and implications of the use of hypnotic psychotherapy, coupled with cognitive behavioral treatment programs, for treating sex offenders. (Contains 2 tables.)

  4. A suicide involving intraperitoneal injection of pentobarbital.

    PubMed

    Hangartner, Sarah; Steiner, Jasmin; Dussy, Franz; Moeckli, Regula; Gerlach, Kathrin; Briellmann, Thomas

    2016-09-01

    We present an unusual case of suicide by intraperitoneal injection of pentobarbital, an overdose of zolpidem and the intake of diazepam, ethanol and other psychoactive substances. The autopsy and specimen collection were conducted in a 10 to 18 h postmortem interval. The toxicological analysis revealed a significantly higher pentobarbital concentration in femoral blood compared to cardiac blood (36 vs. 15 mg/L). On the contrary, zolpidem and diazepam concentrations in cardiac blood (2700 and 590 µg/L) were found to be significantly higher than in femoral blood (1500 and 230 µg/L). These findings point to a postmortem redistribution with a distinct gradient from areas of high drug concentrations in the gastrointestinal tract (zolpidem and diazepam) and the injection site (pentobarbital) to peripheral tissue. Ethanol concentration was 0.95 ‰ which amplified the CNS depression. The choice of this unusual suicide method was associated with the deceased's former job as a veterinarian's assistant. In veterinary medicine, the intraperitoneal injection of a lethal dose of pentobarbital is quite commonly performed to euthanise small animals. Intraperitoneal injection is rare as route of administration in humans. PMID:26174446

  5. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds.

    PubMed

    Griffiths, Roland R; Johnson, Matthew W

    2005-01-01

    Hypnotic drugs, including benzodiazepine receptor ligands, barbiturates, antihistamines, and melatonin receptor ligands, are useful in treating insomnia, but clinicians should consider the relative abuse liability of these drugs when prescribing them. Two types of problematic hypnotic self-administration are distinguished. First, recreational abuse occurs when medications are used purposefully for the subjective "high." This type of abuse usually occurs in polydrug abusers, who are most often young and male. Second, chronic quasi-therapeutic abuse is a problematic use of hypnotic drugs in which patients continue long-term use despite medical recommendations to the contrary. Relative abuse liability is defined as an interaction between the relative reinforcing effects (i.e., the capacity to maintain drug self-administration behavior, thereby increasing the likelihood of nonmedical problematic use) and the relative toxicity (i.e., adverse effects having the capacity to harm the individual and/or society). An algorithm is provided that differentiates relative likelihood of abuse and relative toxicity of 19 hypnotic compounds: pentobarbital, methaqualone, diazepam, flunitrazepam, lorazepam, GHB (gamma-hydroxybutyrate, also known as sodium oxybate), temazepam, zaleplon, eszopiclone, triazolam, zopiclone, flurazepam, zolpidem, oxazepam, estazolam, diphenhydramine, quazepam, tra-zodone, and ramelteon. Factors in the analysis include preclinical and clinical assessment of reinforcing effects, preclinical and clinical assessment of withdrawal, actual abuse, acute sedation/memory impairment, and overdose lethality. The analysis shows that both the likelihood of abuse and the toxicity vary from high to none across these compounds. The primary clinical implication of the range of differences in abuse liability is that concern about recreational abuse, inappropriate long-term use, or adverse effects should not deter physicians from prescribing hypnotics when clinically

  6. Distinct structural changes in the GABAA receptor elicited by pentobarbital and GABA.

    PubMed

    Muroi, Yukiko; Theusch, Cassandra M; Czajkowski, Cynthia; Jackson, Meyer B

    2009-01-01

    The barbiturate pentobarbital binds to gamma-aminobutyric acid type A (GABA(A)) receptors, and this interaction plays an important role in the anesthetic action of this drug. Depending on its concentration, pentobarbital can potentiate (approximately 10-100 microM), activate (approximately 100-800 microM), or block (approximately 1-10 mM) the channel, but the mechanisms underlying these three distinct actions are poorly understood. To investigate the drug-induced structural rearrangements in the GABA(A) receptor, we labeled cysteine mutant receptors expressed in Xenopus oocytes with the sulfhydryl-reactive, environmentally sensitive fluorescent probe tetramethylrhodamine-6-maleimide (TMRM). We then used combined voltage clamp and fluorometry to monitor pentobarbital-induced channel activity and local protein movements simultaneously in real time. High concentrations of pentobarbital induced a decrease in TMRM fluorescence (F(TMRM)) of labels tethered to two residues in the extracellular domain (alpha(1)L127C and beta(2)L125C) that have been shown previously to produce an increase in F(TMRM) in response to GABA. Label at beta(2)K274C in the extracellular end of the M2 transmembrane helix reported a small but significant F(TMRM) increase during application of low modulating pentobarbital concentrations, and it showed a much greater F(TMRM) increase at higher concentrations. In contrast, GABA decreased F(TMRM) at this site. These results indicate that GABA and pentobarbital induce different structural rearrangements in the receptor, and thus activate the receptor by different mechanisms. Labels at alpha(1)L127C and beta(2)K274C change their fluorescence by substantial amounts during channel blockade by pentobarbital. In contrast, picrotoxin blockade produces no change in F(TMRM) at these sites, and the pattern of F(TMRM) signals elicited by the antagonist SR95531 differs from that produced by other antagonists. Thus, with either channel block by antagonists or

  7. Can motor imagery and hypnotic susceptibility explain Conversion Disorder with motor symptoms?

    PubMed

    Srzich, Alexander J; Byblow, Winston D; Stinear, James W; Cirillo, John; Anson, J Greg

    2016-08-01

    Marked distortions in sense of agency can be induced by hypnosis in susceptible individuals, including alterations in subjective awareness of movement initiation and control. These distortions, with associated disability, are similar to those experienced with Conversion Disorder (CD), an observation that has led to the hypothesis that hypnosis and CD share causal mechanisms. The purpose of this review is to explore the relationships among motor imagery (MI), hypnotic susceptibility, and CD, then to propose how MI ability may contribute to hypnotic responding and CD. Studies employing subjective assessments of mental imagery have found little association between imagery abilities and hypnotic susceptibility. A positive association between imagery abilities and hypnotic susceptibility becomes apparent when objective measures of imagery ability are employed. A candidate mechanism to explain motor responses during hypnosis is kinaesthetic MI, which engages a strategy that involves proprioception or the "feel" of movement when no movement occurs. Motor suppression imagery (MSI), a strategy involving inhibition of movement, may provide an alternate objective measurable phenomenon that underlies both hypnotic susceptibility and CD. Evidence to date supports the idea that there may be a positive association between kinaesthetic MI ability and hypnotic susceptibility. Additional evidence supports a positive association between hypnotic susceptibility and CD. Disturbances in kinaesthetic MI performance in CD patients indicate that MI mechanisms may also underlie CD symptoms. Further investigation of the above relationships is warranted to explain these phenomena, and establish theoretical explanations underlying sense of agency. PMID:27346334

  8. Effects of pentobarbital on upper airway patency during sleep.

    PubMed

    Eikermann, M; Eckert, D J; Chamberlin, N L; Jordan, A S; Zaremba, S; Smith, S; Rosow, C; Malhotra, A

    2010-09-01

    We hypothesised that pentobarbital would improve upper airway mechanics based on an increase in latency to arousal and amplitude of the phasic genioglossus electromyogram (EMG), and a decrease in the active upper airway critical closing pressure (P(crit)). 12 healthy subjects received pentobarbital (100 mg) or placebo in a double-blind, crossover protocol. During wakefulness, we measured the genioglossus reflex response to negative pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep. With basal breathing during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal CO(2) concentration and upper airway resistance were greater; and P(crit) was unaffected (pentobarbital mean ± SD -11.7 ± 4.5 versus placebo -10.25 ± 3.6 cmH(2)O; p = 0.11). Pentobarbital increased the time to arousal (297 ± 63s versus 232 ± 67 s; p<0.05), at which time phasic genioglossus EMG was higher (6.2 ± 4.8% maximal versus 3.1 ± 3%; p<0.05) as were CO(2) levels. The increase in genioglossus EMG after CO(2) administration was greater after pentobarbital versus placebo. Pentobarbital did not affect the genioglossus negative-pressure reflex. Pentobarbital increases the time to arousal and stimulates genioglossus muscle activity, but it also increases upper airway resistance during sleep. PMID:20032012

  9. Effects of pentobarbital on upper airway patency during sleep

    PubMed Central

    Eikermann, M.; Eckert, D.J.; Chamberlin, N.L.; Jordan, A.S.; Zaremba, S.; Smith, S.; Rosow, C.; Malhotra, A.

    2012-01-01

    We hypothesised that pentobarbital would improve upper airway mechanics based on an increase in latency to arousal and amplitude of the phasic genioglossus electromyogram (EMG), and a decrease in the active upper airway critical closing pressure (Pcrit). 12 healthy subjects received pentobarbital (100 mg) or placebo in a double-blind, crossover protocol. During wakefulness, we measured the genioglossus reflex response to negative pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep. With basal breathing during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal CO2 concentration and upper airway resistance were greater; and Pcrit was unaffected (pentobarbital mean±sd -11.7±4.5 versus placebo -10.25±3.6 cmH2O; p=0.11). Pentobarbital increased the time to arousal (297±63s versus 232±67 s; p<0.05), at which time phasic genioglossus EMG was higher (6.2±4.8% maximal versus 3.1±3%; p<0.05) as were CO2 levels. The increase in genioglossus EMG after CO2 administration was greater after pentobarbital versus placebo. Pentobarbital did not affect the genioglossus negative-pressure reflex. Pentobarbital increases the time to arousal and stimulates genioglossus muscle activity, but it also increases upper airway resistance during sleep. PMID:20032012

  10. Patterns of hypnotic response, revisited.

    PubMed

    Kihlstrom, John F

    2015-12-15

    It has long been speculated that there are discrete patterns of responsiveness to hypnotic suggestions, perhaps paralleling the factor structure of hypnotizability. An earlier study by Brenneman and Kihlstrom (1986), employing cluster analysis, found evidence for 12 such profiles. A new study by Terhune (2015), employing latent profile analysis, found evidence for three such patterns among highly hypnotizable subjects, and a fourth comprising subjects of medium hypnotizability. Some differences between the two studies are described. Convincing identification of discrete "types" of high hypnotizability, such as dissociative and nondissociative, may require a larger dataset than is currently available, but also data pertaining directly to divisions in conscious awareness and experienced involuntariness. PMID:26551995

  11. Pentobarbital anesthesia alters pulmonary vascular response to neural antagonists.

    PubMed

    Nyhan, D P; Goll, H M; Chen, B B; Fehr, D M; Clougherty, P W; Murray, P A

    1989-05-01

    We investigated the effects of pentobarbital sodium anesthesia on vasoregulation of the pulmonary circulation. Our specific objectives were to 1) assess the net effect of pentobarbital on the base-line pulmonary vascular pressure-to-cardiac index (P/Q) relationship compared with that measured in conscious dogs, and 2) determine whether autonomic nervous system (ANS) regulation of the intact P/Q relationship is altered during pentobarbital. P/Q plots were constructed by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Pentobarbital (30 mg/kg iv) had no net effect on the base-line P/Q relationship. In contrast, changes in the conscious intact P/Q relationship in response to ANS antagonists were markedly altered during pentobarbital. Sympathetic alpha-adrenergic receptor block with prazosin caused active pulmonary vasodilation (P less than 0.01) in conscious dogs but caused vasoconstriction (P less than 0.01) during pentobarbital. Sympathetic beta-adrenergic receptor block with propranolol caused active pulmonary vasoconstriction (P less than 0.01) in both groups, but the magnitude of the vasoconstriction was attenuated (P less than 0.05) during pentobarbital at most levels of Q. Finally, cholinergic receptor block with atropine resulted in active pulmonary vasodilation (P less than 0.01) in conscious dogs, whereas vasoconstriction (P less than 0.01) was observed during pentobarbital. Thus, although pentobarbital had no net effect on the base-line P/Q relationship measured in conscious dogs, ANS regulation of the intact pulmonary vascular P/Q relationship was altered during pentobarbital anesthesia. PMID:2566280

  12. [Effect of pentobarbital on the biothermic individuality of growing rats and during instrumental conditioning in heat].

    PubMed

    Rapaport, A

    1977-01-01

    At the dosis of 12,5 mg by kg and in 30 growing white rats, pentobarbital acts by shortening the reaction time, by inducing a short period of psychomotor instrumental activity and after a latency of 5 to 20 mn by depressing the total reserve of instrumental activity acquired before this sessions under physiological serum or caffein injections state dependent larning in heat. PMID:143988

  13. Effect of an imidazobenzodiazepine, Ro15-4513, on the incoordination and hypothermia produced by ethanol and pentobarbital.

    PubMed

    Hoffman, P L; Tabakoff, B; Szabó, G; Suzdak, P D; Paul, S M

    1987-08-01

    The imidazobenzodiazepine, Ro15-4513, which is a partial inverse agonist at brain benzodiazepine receptors, reversed the incoordinating effect of ethanol in mice, as measured on an accelerating Rotarod. This effect was blocked by benzodiazepine receptor antagonists. In contrast, Ro15-4513 had no effect on ethanol-induced hypothermia in mice. However, Ro15-4513 reversed the hypothermic effect of pentobarbital, and, at a higher dose, also reversed the incoordinating effect of pentobarbital in mice. The data support the hypothesis that certain of the pharmacological effects of ethanol are mediated by actions at the GABA-benzodiazepine receptor-coupled chloride channel. PMID:3600196

  14. [Insomnia therapy and withdrawal of hypnotics].

    PubMed

    Garma, L; Widlöcher, D; Scherrer, J

    1982-11-18

    The aim of this study is to evaluate the efficiency of a treatment prescribed, in the course of an hospital consultation for sleep pathology, to patients suffering from chronic insomnia not improved by longstanding and sustained medication with hypnotic drugs. The basis of the treatment is a progressive but total withdrawal of hypnotics in so far taken regularly. The withdrawal of hypnotics was prescribed to 79 patients: 33 aged 17 to 39 years (group 1, mean age 30) and 46 aged 40 to 70 years (group 2, mean age 51). 41 showed primary psychophysiological insomnia and 28 showed insomnia associated with psychiatric disorders. In patients of group 1, the average durations were 8 years for insomnia and 3 years for sustained hypnotic use; these durations were 15 and 5 years respectively in patients of group 2. Hypnotic drug withdrawal was achieved without placebos in 3 months in group 1 patients and 5 months in group 2 patients. 65 patients completely stopped the continual use of hypnotics. Subjective improvement of insomnia was reported by 51 of these patients (as well as by 6 patients who were given simultaneous antidepressant therapy). 16 of the 51 improved patients have resorted to hypnotics occasionally (at intervals of 10 days or more). After complete withdrawal, patients went on consulting for various lengths of time: 5 months average for group 1, 14 months average for group 2. This study of a fairly large group of insomniacs shows the frequent ineffectiveness of a sustained use of currently available hypnotics. It also shows that two times out of three the complete stop of sustained hypnotic medication proved beneficial to the patient. PMID:6297032

  15. Primate study suggests pentobarbital may help protect the brain during radiation therapy

    SciTech Connect

    Skolnick, A.

    1990-08-01

    Radiation therapy, an often indispensable treatment for a wide range of brain tumors, is a double-edged sword, especially when used to treat children. Research reported at the 72nd Annual Meeting of the Endocrine Society, in Atlanta, Ga., now suggests that pentobarbital and perhaps other barbiturates may help protect the brain from radiation-induced damage, especially to the pituitary and hypothalmus, where such damage can lead to serious, life-long problems for children. Jeffrey J. Olson, MD, now assistant professor of neurosurgery at Emory University School of Medicine, Atlanta, reported the results of a study of the radioprotective effects of pentobarbital on the brain of a primate, which he and colleagues at the National Institute of Neurological Disorders and Stroke recently completed.

  16. Influence of zolpidem, a novel hypnotic, on the intermediate-stage and paradoxical sleep in the rat.

    PubMed

    Gottesmann, C; Trefouret, S; Depoortere, H

    1994-02-01

    Paradoxical sleep (PS) in mice, rats, and cats is preceded and sometimes followed by a short-lasting stage characterized by cortical high-amplitude spindles and hippocampal low-frequency theta rhythm. This intermediate stage (IS) seems to correspond to a transient functional disconnection of the forebrain from the brainstem. Pentobarbital and benzodiazepines greatly extend IS at the expense of PS, which is suppressed. Zolpidem, a new imidazopyridine hypnotic, was studied at 2.5, 5, and 7.5 mg/kg IP. At 2.5 mg/kg, which is already a true hypnotic dose, it only decreased PS during the first 2 h of recording with a rebound during the following 4 h of recording. At 5 mg/kg, zolpidem increased the number and total duration of IS episodes, increased IS episodes not followed by PS, and increased PS latency of occurrence. PS amount was decreased during the first three h with a rebound in the next 3 h. At 7.5 mg/kg, the total amount of PS was also decreased. The eye movement number and theta rhythm frequency of PS were unchanged. These results show that zolpidem produces less disruption of the association between IS and PS than do previous hypnotics. PMID:8146229

  17. Hypnotically enhanced dreaming to achieve symptom reduction: a case study of 11 children and adolescents.

    PubMed

    Linden, Julie H; Bhardwaj, Anuj; Anbar, Ran D

    2006-04-01

    Theories about dreams have shaped our thinking about mind-body unity and the influence of thought on the body. In this article, the authors review the sparse literature regarding the use of hypnosis with children's dreams and nightmares, summarize how hypnotically induced dreams have been used to resolve psychological symptoms, and note five themes in the literature worthy of further investigation. Building on the value of both dreams and hypnosis for working through conflicts, the authors united mind-body medicine and hypnotically induced dreaming in a pediatric pulmonary practice. A case series is presented of 11 patients who were offered an opportunity to review their reported nightmares through hypnosis in order to uncover their potential meaning. The recurrent nightmares among these patients decreased greatly in frequency or resolved following the hypnosis enhanced dream review. Thus, we demonstrate that hypnotically induced dream review may be useful in a pediatric population. PMID:16696559

  18. Suggestibility, expectancy, trance state effects, and hypnotic depth: I. Implications for understanding hypnotism.

    PubMed

    Pekala, Ronald J; Kumar, V K; Maurer, Ronald; Elliott-Carter, Nancy; Moon, Edward; Mullen, Karen

    2010-04-01

    This paper reviews the relationships between trance or altered state effects, suggestibility, and expectancy as these concepts are defined in the theorizing of Weitzenhoffer (2002), Holroyd (2003), Kirsch (1991), and others, for the purpose of demonstrating how these concepts can be assessed with the PCI-HAP (Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure; Pekala, 1995a, b). In addition, how the aforementioned variables may relate to the nature of hypnosis/hypnotism as a function of self-reported hypnotic depth are discussed, along with how the PCI-HAP may be used as a means to measure hypnotic responsivity from a more phenomenological state perspective, in contrast to more traditional behavioral trait assessment instruments like the Harvard, the Stanford C, or the HIP. A follow-up paper (Pekala, Kumar, Maurer, Elliott-Carter, Moon, & Mullen, 2010) will present research data on the PCI-HAP model and how this model can be useful for better understanding hypnotism. PMID:20499542

  19. Imagination and dissociation in hypnotic responding.

    PubMed

    Bowers, K S

    1992-10-01

    A neodissociative model of mind is better equipped than a social-psychological model to deal with the complexities of hypnosis, and of human behavior generally. It recognizes, as Coe's (1992) model does not, that behavior can be more automatically activated than strategically enacted. In particular, Coe's emphasis on human behavior as purposeful and goal directed does not distinguish between goal-directed behavior that serves a purpose, and goal-directed behavior that is performed on purpose. It is this distinction that permits goal-directed behavior to be dissociated from a person's conscious plans and intentions. In addition to offering a critique of Coe's "limited process" view of hypnosis, 4 main points are made in the interest of developing a slightly modified, neodissociation view of hypnosis. First, it is argued that goal-directed fantasies are more limited in their ability to mediate hypnotic responding than is commonly appreciated; as well, they do not seem to account for the nonvolitional quality of hypnotic responding. Second, it is argued that hypnotic ability is not unidimensional, with compliance and social influence more apt to account for the low than for the high hypnotizable's responsiveness to suggestion. Third, compared to low hypnotizables, the hypnotic responsiveness of high hypnotizables seems more likely to result from dissociated control. In other words, for high hypnotizables, hypnotic suggestions may often directly activate subsystems of cognitive control. Consequently, the need for executive initiative and effort to produce hypnotically suggested behavior is minimized, and such responses are therefore experienced as nonvolitional. Fourth and finally, while goal-directed fantasies typically accompany hypnotically suggested responses, they are in many cases more a marker of dissociated control than a mediator of suggested effects. PMID:1468834

  20. What Can a Hypnotic Induction Do?

    PubMed

    Woody, Erik; Sadler, Pamela

    2016-10-01

    In contrast to how recent definitions of hypnosis describe the induction, a work-sample perspective is advocated that characterizes the induction as an initial, stage-setting phase encompassing everything in a hypnotic session up to the first hypnotic suggestion of particular relevance to the therapeutic or research goals at hand. Four major ways are then discussed in which the induction could affect subsequent hypnotic responses: It may provide information about how subsequent behaviors are to be enacted; it may provide cues about the nature of the interpersonal interaction to be expected in hypnosis; it may provide meta-suggestions, defined as suggestive statements intended to enhance responses to subsequent hypnotic suggestions; and it may provide a clear transition to help allow new behaviors and experiences to emerge. Several ideas for future research are advanced, such as mapping hypnosis style onto the interpersonal circumplex, evaluating whether attentional-state changes measured at the end of the induction actually mediate subsequent hypnotic responsiveness, and systematically examining the impact of ritual-like aspects of inductions. PMID:27586044

  1. The effects of pentobarbital, ketamine-pentobarbital and ketamine-xylazine anesthesia in a rat myocardial ischemic reperfusion injury model.

    PubMed

    Shekarforoush, Shahnaz; Fatahi, Zahra; Safari, Fatemeh

    2016-06-01

    To achieve reliable experimental data, the side-effects of anesthetics should be eliminated. Since anesthetics exert a variety of effects on hemodynamic data and incidence of arrhythmias, the selection of anesthetic agents in a myocardial ischemic reperfusion injury model is very important. The present study was performed to compare hemodynamic variables, the incidence of ventricular arrhythmias, and infarct size during 30 min of ischemia and 120 min of reperfusion in rats using pentobarbital, ketamine-pentobarbital or ketamine-xylazine anaesthesia. A total of 30 rats were randomly divided into three groups. In group P, pentobarbital (60 mg/kg, intraperitoneally [IP]) was used solely; in group K-P, ketamine and pentobarbital (50 and 30 mg/kg, respectively, IP) were used in combination; and in group K-X, ketamine and xylazine (75 and 5 mg/kg, respectively, IP) were also used in combination. Hemodynamic data and occurrence of ventricular arrhythmias were recorded throughout the experiments. The ischemic area was measured by triphenyltetrazolium chloride staining. The combination of ketamine-xylazine caused bradycardia and hypotension. The greatest reduction in mean arterial blood pressure during ischemia was in the P group. The most stability in hemodynamic parameters during ischemia and reperfusion was in the K-P group. The infarct size was significantly less in the K-X group. Whereas none of the rats anesthetized with ketamine-xylazine fibrillated during ischemia, ventricular fibrillation occurred in 57% of the animals anesthetized with pentobarbital or ketamine-pentobarbital. Because it offers the most stable hemodynamic parameters, it is concluded that the ketamine-pentobarbital anesthesia combination is the best anesthesia in a rat ischemia reperfusion injury model. PMID:26224732

  2. Effects of repeated high dosage of chloral hydrate and pentobarbital sodium anesthesia on hepatocellular system in rats.

    PubMed

    Yu, Jianhong; Sun, Xuehui; Sang, Guifeng

    2015-01-01

    This study aims to investigate the possible effects of repeated high dosage of chloral hydrate and pentobarbital sodium anesthesia on hepatocellular system in rats. Thirty Sprague Dawley rats were randomly divided into 3 groups: control group (group A), chloral hydrate group (group B) and pentobarbital sodium group (group C). Antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione s transferase (GST) and catalase (CAT) activities and thiobarbituric acid-reactive substances (TBARS) level as well as serum biochemical parameters alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (T-BIL) were determined. Liver histopathological examinations were performed at termination. Furthermore, Bax and Bcl-2 expression, and caspase-3 activity were also evaluated. The SOD, GSH-Px, GST and CAT activities significantly decreased but TBARS levels increased in group B and C compared with group A. Hepatic injury was evidenced by a significant increase in serum ALT, AST and ALP activities in group B and C, which also confirmed by the histopathological alterations. Moreover, administration of chloral hydrate and pentobarbital sodium could induce certain hepatic apoptosis accompanied by the upregulated Bax expression, the downregulated Bcl-2 expression and Bcl-2/Bax ratio, and the increase of caspase-3 activity. Repeated high dosage of chloral hydrate and pentobarbital sodium anesthesia could produce hepatotoxicity. PMID:26379846

  3. Analgesic and hypnotic activities of Laghupanchamula: A preclinical study

    PubMed Central

    Ghildiyal, Shivani; Gautam, Manish K.; Joshi, Vinod K.; Goel, Raj K.

    2014-01-01

    Background: In Ayurvedic classics, two types of Laghupanchamula -five plant roots (LP) have been mentioned containing four common plants viz. Kantakari, Brihati, Shalaparni, and Prinshniparni and the fifth plant is either Gokshura (LPG) or Eranda (LPE). LP has been documented to have Shothahara (anti-inflammatory), Shulanashka (analgesic), Jvarahara (antipyretic), and Rasayana (rejuvenator) activities. Aim: To evaluate the acute toxicity (in mice), analgesic and hypnotic activity (in rats) of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE). Materials and Methods: LPEG and LPEE were prepared separately by using 50% ethanol following the standard procedures. A graded dose (250, 500 and 1000 mg/kg) response study for both LPEE and LPGE was carried out for analgesic activity against rat tail flick response which indicated 500 mg/kg as the optimal effective analgesic dose. Hence, 500 mg/kg dose of LPEE and LPGE was used for hot plate test and acetic acid induced writhing model in analgesic activity and for evaluation of hypnotic activity. Results: Both the extracts did not produce any acute toxicity in mice at single oral dose of 2.0 g/kg. Both LPGE and LPEE (250, 500, and 1000 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 60 min as evidenced by increased latency period in tail-flick method by 25.1-62.4% and 38.2-79.0% respectively. LPGE and LPEE (500 mg/kg) increased reaction time in hot-plate test at peak 60 min analgesic effect by 63.2 and 85.8% and reduction in the number of acetic acid-induced writhes by 55.9 and 65.8% respectively. Both potentiated pentobarbitone-induced hypnosis as indicated by increased duration of sleep in treated rats. Conclusion: The analgesic and hypnotic effects of LP formulations authenticate their uses in Ayurvedic system of Medicine for painful conditions. PMID:25364205

  4. Brain correlates of hypnotic paralysis-a resting-state fMRI study.

    PubMed

    Pyka, M; Burgmer, M; Lenzen, T; Pioch, R; Dannlowski, U; Pfleiderer, B; Ewert, A W; Heuft, G; Arolt, V; Konrad, C

    2011-06-15

    Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities. PMID:21497656

  5. [An analysis of subjective perception of hypnotic state].

    PubMed

    Umanskiĭ, S V; Utkin, V A

    2006-01-01

    The results of the study of hypnotic states on the basis of subjective reflections of their perceptions by patients are presented. The factor map of the features of hypnotic states formation is obtained and some variants of the course of hypnotic states are determined in light of domination of the certain factors. PMID:16457131

  6. Top-down regulation of left temporal cortex by hypnotic amusia for rhythm: a pilot study on mismatch negativity.

    PubMed

    Facco, Enrico; Ermani, Mario; Rampazzo, Patrizia; Tikhonoff, Valérie; Saladini, Marina; Zanette, Gastone; Casiglia, Edoardo; Spiegel, David

    2014-01-01

    To evaluate the effect of hypnotically induced amusia for rhythm (a condition in which individuals are unable to recognize melodies or rhythms) on mismatch negativity (MMN), 5 highly (HH) and 5 poorly (LH) hypnotizable nonmusician volunteers underwent MMN recording before and during a hypnotic suggestion for amusia. MMN amplitude was recorded using a 19-channel montage and then processed using the low-resolution electromagnetic tomography (LORETA) to localize its sources. MMN amplitude was significantly decreased during hypnotic amusia (p < .04) only in HH, where the LORETA maps of MMN showed a decreased source amplitude in the left temporal lobe, suggesting a hypnotic top-down regulation of activity of these areas and that these changes can be assessed by neurophysiological investigations. PMID:24568321

  7. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) (b)(1) Specifications. Chloral hydrate, pentobarbital, and magnesium...

  8. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) (b)(1) Specifications. Chloral hydrate, pentobarbital, and magnesium...

  9. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) (b)(1) Specifications. Chloral hydrate, pentobarbital, and magnesium...

  10. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) (b)(1) Specifications. Chloral hydrate, pentobarbital, and magnesium...

  11. Insomnia in children: when are hypnotics indicated?

    PubMed

    Younus, Mohammed; Labellarte, Michael J

    2002-01-01

    Insomnia in children is a nonspecific impairing symptom that may be the result of normal developmental changes, psychosocial duress, a sleep disorder, a psychiatric disorder, other medical disorders, substance misuse, or an adverse effect of medication. Careful clinical assessment of insomnia in children may include the use of symptom rating scales, laboratory testing, or other medical assessment. Short- and long-term treatment of insomnia in children involves management of etiological factors and associated syndromes. Controlled treatment studies of pediatric insomnia are limited to <10 published studies of psychosocial and/or psychopharmacological treatment in young children. Directive parent education and behavior modification techniques have been effective in short-term treatment of insomnia in young children, and may be the preferred treatment of extrinsic insomnia, as well as an important adjunctive treatment of any insomnia symptoms. Two benzodiazepines [flurazepam and delorazepam (chlordesmethyldiazepam)], one antihistamine (niaprazine) and one phenothiazine [alimemazine (trimeprazine)] have been shown to be effective in the short-term treatment of insomnia in young children, although none of these agents have US Food and Drug Administration approval for pediatric insomnia. Short-acting benzodiazepines may have a role in the brief treatment of pediatric insomnia associated with an anxiety or mood disorder, psychosis, aggression, medication- induced activation, or anticipatory anxiety associated with a medical procedure. However, tachyphylaxis and risk of misuse preclude the long-term use of benzodiazepines for the treatment of insomnia in children. Newer hypnotics, which appear better tolerated than the benzodiazepines in studies of adults, may have a role when combined with psychosocial treatments of pediatric insomnia. Treatment of intrinsic pediatric insomnia may additionally involve chronotherapy or medical management. PMID:12038875

  12. Time-course of motor inhibition during hypnotic paralysis: EEG topographical and source analysis.

    PubMed

    Cojan, Yann; Archimi, Aurélie; Cheseaux, Nicole; Waber, Lakshmi; Vuilleumier, Patrik

    2013-02-01

    Cognitive hypotheses of hypnotic phenomena have proposed that executive attentional systems may be either inhibited or overactivated to produce a selective alteration or disconnection of some mental operations. Recent brain imaging studies have reported changes in activity in both medial (anterior cingulate) and lateral (inferior) prefrontal areas during hypnotically induced paralysis, overlapping with areas associated with attentional control as well as inhibitory processes. To compare motor inhibition mechanisms responsible for paralysis during hypnosis and those recruited by voluntary inhibition, we used electroencephalography (EEG) to record brain activity during a modified bimanual Go-Nogo task, which was performed either in a normal baseline condition or during unilateral paralysis caused by hypnotic suggestion or by simulation (in two groups of participants, each tested once with both hands valid and once with unilateral paralysis). This paradigm allowed us to identify patterns of neural activity specifically associated with hypnotically induced paralysis, relative to voluntary inhibition during simulation or Nogo trials. We used a topographical EEG analysis technique to investigate both the spatial organization and the temporal sequence of neural processes activated in these different conditions, and to localize the underlying anatomical generators through minimum-norm methods. We found that preparatory activations were similar in all conditions, despite left hypnotic paralysis, indicating preserved motor intentions. A large P3-like activity was generated by voluntary inhibition during voluntary inhibition (Nogo), with neural sources in medial prefrontal areas, while hypnotic paralysis was associated with a distinctive topography activity during the same time-range and specific sources in right inferior frontal cortex. These results add support to the view that hypnosis might act by enhancing executive control systems mediated by right prefrontal areas, but

  13. Approaches in the evaluation of hypnotics

    PubMed Central

    Purpura, R. P.

    1981-01-01

    1 The evaluation of an hypnotic may be approached from the view that insomnia is a primary disease or the symptom of an underlying emotional or physical problem. 2 The two approaches have been used in the investigation of triazolam. PMID:6133533

  14. 21 CFR 522.1704 - Sodium pentobarbital injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... sterile and contains in each milliliter 64.8 milligrams of sodium pentobarbital. (2) Sponsor. See No. 000061 in § 510.600(c) of this chapter. (3) Conditions of use. (i) The drug is indicated for use as a... restricts this drug to use by or on the order of a licensed veterinarian. (b)...

  15. Quantitation of amobarbital, butalbital, pentobarbital, phenobarbital, and secobarbital in urine, serum, and plasma using gas chromatography-mass spectrometry (GC-MS).

    PubMed

    Johnson, Leonard L; Garg, Uttam

    2010-01-01

    Barbiturates are central nervous system depressants with sedative and hypnotic properties. Some barbiturates, with longer half-lives, are used as anticonvulsants. Their mechanism of action includes activation of gamma-aminobutyric acid (GABA) mediated neuronal transmission inhibition. Clinically used barbiturates include amobarbital, butalbital, pentobarbital, phenobarbital, secobarbital, and thiopental. Besides their therapeutic use, barbiturates are commonly abused. Their analysis is useful for both clinical and forensic proposes. Gas chromatography mass spectrometry is a commonly used method for the analysis of barbiturates. In the method described here, barbiturates from serum, plasma, or urine are extracted using an acidic phosphate buffer and methylene chloride. Barbital is used as an internal standard. The organic extract is dried and reconstituted with mixture of trimethylanilinium hydroxide (TMAH) and ethylacetate. The extract is injected into a gas chromatogram mass spectrometer where it undergoes "flash methylation" in the hot injection port. Selective ion monitoring and relative retention times are used for the identification and quantitation of barbiturates. PMID:20077060

  16. Cajal's brief experimentation with hypnotic suggestion.

    PubMed

    Stefanidou, Maria; Solà, Carme; Kouvelas, Elias; del Cerro, Manuel; Triarhou, Lazaros C

    2007-01-01

    Spanish histologist Santiago Ramón y Cajal, one of the most notable figures in Neuroscience, and winner, along with Camillo Golgi, of the 1906 Nobel Prize in Physiology or Medicine for his discoveries on the structure of the nervous system, did not escape experimenting with some of the psychiatric techniques available at the time, mainly hypnotic suggestion, albeit briefly. While a physician in his thirties, Cajal published a short article under the title, "Pains of labour considerably attenuated by hypnotic suggestion" in Gaceta Médica Catalana. That study may be Cajal's only documented case in the field of experimental psychology. We here provide an English translation of the original Spanish text, placing it historically within Cajal's involvement with some of the key scientific and philosophical issues at the time. PMID:17966053

  17. Hypnotic Induction: Enhancing Trance or Mostly Myth?

    PubMed

    Reid, David B

    2016-10-01

    Hypnosis has often, and primarily, been portrayed as a mystical means that controls and exploits vulnerable and defenseless people. Sources accused of perpetuating hypnosis myths and misconceptions have included numerous media productions and stage demonstrations at state fairs and festivals. Ironically, one largely unexamined potential culprit disseminating misinformation about hypnosis is the field of clinical hypnosis itself. This article not only questions the legitimacy of the term "hypnotic induction" and its derivatives but also explores the potential impact these terms have on the perpetuation of hypnosis myths and misconceptions. Through an examination of a selective history of hypnotic induction, the customary language of hypnosis, and information promoted by professional hypnosis societies, some of the contributing terminology is identified. Alternative terms that more appropriately embody the manifestation of trance are offered and discussed. PMID:27586043

  18. Brain Oscillations and Diurnal Variations in Hypnotic Responsiveness--A Commentary on "Diurnal Variations in Hypnotic Responsiveness: Is There an Optimal Time to be Hypnotized?".

    PubMed

    Jensen, Mark P

    2016-01-01

    A recent study published in the International Journal of Clinical and Experimental Hypnosis reported an interesting diurnal pattern of hypnotic responsivity; specifically, the authors found higher hypnotic responsiveness in a large sample of undergraduates in the morning and early evening. However, they did not have an explanation for this pattern of findings. This pattern is consistent, however, with the theta hypothesis of hypnotic responsivity. Further examination of the associations between brain oscillations and response to hypnosis is needed to determine if specific oscillations such as theta (a) actually facilitate response to some hypnotic suggestions, (b) merely reflect hypnotic responding, or (c) reflect another factor that itself plays a causal role in response to hypnosis. PMID:26599996

  19. Identification and differentiation of barbiturates, other sedative-hypnotics and their metabolites in urine integrated in a general screening procedure using computerized gas chromatography-mass spectrometry.

    PubMed

    Maurer, H H

    1990-09-14

    A gas chromatographic-mass spectrometric procedure is described for the identification and differentiation of sedative-hypnotics and their metabolites in urine. The following 24 barbiturates and thirteen other hypnotics could be detected: acecarbromal, allobarbital, amobarbital, aprobarbital, barbital, brallobarbital, bromisoval, (sec)butabarbital, butalbital, butobarbital, carbromal, clomethiazole, crotylbarbital, cyclobarbital, cyclopentobarbital, diethylallylacetamide, dipropylbarbital, glutethimide, guaifenesin, ethinamate, heptabarbital, hexobarbital, meprobamate, methaqualone, metharbital, methohexital, methylphenobarbital, methyprylone, pentobarbital, phenobarbital, propallylonal, pyrithyldione, secobarbital, thiobutabarbital, thiopental, vinbarbital and vinylbital. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs detecting over 300 drugs and over 1000 of their metabolites. It includes cleavage of conjugates by acid hydrolysis, isolation by liquid-liquid extraction, derivatization by acetylation, separation by capillary gas chromatography, and identification by computerized mass spectrometry. Using mass chromatography with the selected ions m/z 83, 117, 141, 167, 169, 207, 221 and 235, the presence of barbiturates, other hypnotics and/or their metabolites was indicated. The identity of positive signals in the reconstructed mass chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The sample preparation, mass chromatograms, reference mass spectra and gas chromatographic retention indices are documented. PMID:2079506

  20. An unusual case of relay pentobarbital toxicosis in a dog.

    PubMed

    Bischoff, Karyn; Jaeger, Robin; Ebel, Joseph G

    2011-09-01

    Sodium pentobarbital and phenytoin are common constituents of veterinary euthanasia solutions in the United States. Relay, or secondary, barbiturate toxicosis has been reported in carnivorous animals that have fed from the carcasses of euthanized livestock. This case report presents barbiturate toxicosis in a dog. A 2-year-old female spayed Australian shepherd presented comatose 2 h after ingesting an unknown substance on the beach. The material was retrieved from the stomach by gastric lavage and visually identified as fish or other animal tissue. The dog recovered with symptomatic and supportive therapy and was released on the third day of hospitalization. Tissue found on the beach near where the dog walked and a urine sample from the dog were analyzed by gas chromatography/mass spectrometry. Both samples were positive for pentobarbital and phenytoin. The tissue was consistent with mammalian blubber based on gross and histological examination. Three weeks previously, a juvenile humpback whale had stranded on the beach where the dog had ingested the unknown substance. The whale had been euthanized with a barbiturate solution, necropsied, and removed from the beach. It was not definitively determined that the pentobarbital-containing blubber ingested by the dog was from the euthanized whale, but that was the most likely source. Although attempts were made to remove the whale's remains from the beach, practical considerations made complete removal challenging, if not impossible. PMID:21660622

  1. Effect of pentobarbital anesthesia on vulnerability to ventricular fibrillation.

    PubMed

    Dawson, A K; Leon, A S; Taylor, H L

    1980-09-01

    Ventricular fibrillation threshold (VFT), frequently determined in dogs during pentobarbital sodium anesthesia, usually is replaced by a single repetitive extrasystole threshold (SRET) or a multiple repetitive extrasystole threshold (MRET) determination in conscious animals and in the human being. In the present study SRET, MRET, and VFT were determined initially in 39 pentobarbital sodium-anesthetized dogs. One week later these three thresholds were redetermined during anesthesia in 13 of the 39 dogs (control group). In the remaining 26 dogs (experimental group), thresholds were redetermined while the dogs were conscious. Significant changes in threshold values occurred only in the experimental group for VFT (P < 0.001) and MRET (P < 0.02). The square of the linear correlation coefficient showed conscious state MRET to be a good predictor of conscious state VFT (R2 = 0.90). Conscious state SRET and anesthetized state VFT showed less predictiveness for the conscious VFT (R2 = 0.72 and 0.51, respectively). These data indicate that MRET may be preferable to SRET as an index of VFT. The SRET, MRET, and VFT determined during pentobarbital anesthesia may not accurately reflect the value of these parameters in the conscious animal. PMID:7435588

  2. Consumer hypnotic-like suggestibility: possible mechanism in compulsive purchasing.

    PubMed

    Prete, M Irene; Guido, Gianluigi; Pichierri, Marco

    2013-08-01

    The authors hypothesize a concept, Consumer Hypnotic-Like Suggestibility (CHLS), defined as an altered state of consciousness, as a state causing a tendency to respond positively to messages aimed at inducing consumers to make unplanned purchases. This study aims to investigate the associations of CHLS with interpersonal variables and compulsive purchasing--a frequent and uncontrollable preoccupation with buying or impulses to buy. A study was conducted on a sample of 232 subjects (n = 111 men; M age = 41 yr.), through the administration of a questionnaire, which measured: CHLS, compulsive purchasing, consumer susceptibility to interpersonal influence (the necessity to enhance one's image in the opinion of others through the consumption of products), and consumer atmospherics, i.e., environmental stimuli known to influence purchasing decisions. Modeling and mediation analyses suggested that internal and external drivers--Consumer Susceptibility to Interpersonal Influence and atmospherics--are positively related to CHLS which affects compulsive purchasing. PMID:24340808

  3. Smoking Cessation: Uni-Modal and Multi-Modal Hypnotic and Non-Hypnotic Approaches.

    ERIC Educational Resources Information Center

    Habicht, Manuela H.

    A survey of Queensland's population in 1993 determined that 24% of the adults were smokers. National data compiled in 1992 indicated that 72% of the drug-related deaths were related to tobacco use. In light of the need for effective smoking cessation approaches, a literature review was undertaken to determine the efficacy of hypnotic and…

  4. Learning and cross drug effects: thermic effects of pentobarbital and amphetamine.

    PubMed

    Hinson, R E; Rhijnsburger, M

    1984-06-25

    The effects of environmental cues explicitly paired or unpaired with pentobarbital on the thermic effects of pentobarbital and amphetamine were investigated. Rats received 19 injections of pentobarbital in a distinctive environment and were subsequently tested for the thermic effects of pentobarbital and amphetamine in the distinctive environment, another environment previously associated only with saline, or in the colony room not previously associated with injections. Rats tested in the context of the environmental cues previously associated with pentobarbital were tolerant to the hypothermic effect of pentobarbital, but rats tested in the environment previously associated only with saline or in the colony room were not tolerant. Pentobarbital-experienced rats administered amphetamine in the context of the usual pentobarbital cues exhibited an exaggerated hyperthermic reaction compared to previously drug-naive rats administered amphetamine. Pentobarbital-experienced rats injected with amphetamine in the homeroom exhibited a smaller hyperthermic response than previously drug-naive rats administered amphetamine in the home room. These results demonstrate that an animal's response to a drug can be affected by cues paired and unpaired with drug administration. PMID:6738300

  5. Effects of hypnotic drugs on performance before and after sleep

    NASA Technical Reports Server (NTRS)

    Kales, A.; Bixler, E. O.; Kales, J. D.

    1975-01-01

    The effects of various hypnotics on sleep stage parameters and on the parameters of effectiveness were evaluated along with the effects of several commonly used yet distinctly different hypnotics on daytime performance. The effects on daytime performance of two nonhypnotics commonly used in the space program were also examined.

  6. Hypnotics and the control of breathing; a review

    PubMed Central

    Cohn, M. A.

    1983-01-01

    1 Hypnotics are central depressants. In sufficient doses, they suppress respiration, and so their effects on respiration are important considerations in their safety. 2 The paper reviews mechanisms of respiratory control and methods of assessment, the effects of hypnotics on control of breathing and new methods of non-invasive respiratory monitoring. PMID:6140945

  7. Hypnotic responsivity of the deaf: the development of the University of Tennessee Hypnotic Susceptibility Scale for the Deaf.

    PubMed

    Repka, R J; Nash, M R

    1995-07-01

    The purpose of these two studies was to develop and test a measure that assesses the hypnotic responsivity of deaf individuals. The University of Tennessee Hypnotic Susceptibility Scale for the Deaf (UTHSS:D) is a signed, videotaped version of a standard hypnotic induction with 12 standard suggestions. Experiment 1 compared the behavioral and subjective hypnotic responsivity of deaf and hearing individuals using the UTHSS:D and the Field Depth Inventory (FDI), respectively. As compared to hearing subjects, deaf participants were found to be less responsive to hypnosis when assessed behaviorally (UTHSS:D) and equally responsive to hypnosis when assessed subjectively (FDI). Experiment 2 undertook a more comprehensive examination of the hypnotic responsivity of deaf individuals, using hearing individuals as controls. Three dimensions of hypnosis responsivity were assessed: behavioral (UTHSS:D), subjective (FDI), and interpersonal (Archaic Involvement Measure). Additionally, correlates of hypnotic responsivity (absorption, attitudes, expectations) were examined for the two groups. In Experiment 2, no significant differences were found between the deaf and hearing participant groups on any measures of hypnotic responsivity or on any measure of the correlates of hypnotic responsivity. PMID:7635582

  8. Hypnotic Taper with or without Self-Help Treatment of Insomnia: A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Belleville, Genevieve; Guay, Catherine; Guay, Bernard; Morin, Charles M.

    2007-01-01

    This study aimed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment (CBT) for insomnia. Fifty-three adult chronic users of hypnotics were randomly assigned to an 8-week hypnotic taper program, used alone or combined with a self-help CBT. Weekly hypnotic use decreased in both…

  9. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chloral hydrate, pentobarbital, and magnesium... FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate. (a) Specifications. Each milliliter of solution contains 42.5 milligrams (mg) of chloral hydrate, 8.86 mg...

  10. 21 CFR 522.2444b - Sodium thiopental, sodium pentobarbital for injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium thiopental, sodium pentobarbital for... FORM NEW ANIMAL DRUGS § 522.2444b Sodium thiopental, sodium pentobarbital for injection. (a) Specifications. Each gram of the drug contains 750 milligrams of sodium thiopental and 250 milligrams of...

  11. 21 CFR 522.2444b - Sodium thiopental, sodium pentobarbital for injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium thiopental, sodium pentobarbital for... FORM NEW ANIMAL DRUGS § 522.2444b Sodium thiopental, sodium pentobarbital for injection. (a) Specifications. Each gram of the drug contains 750 milligrams of sodium thiopental and 250 milligrams of...

  12. 21 CFR 522.2444b - Sodium thiopental, sodium pentobarbital for injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium thiopental, sodium pentobarbital for... FORM NEW ANIMAL DRUGS § 522.2444b Sodium thiopental, sodium pentobarbital for injection. (a) Specifications. Each gram of the drug contains 750 milligrams of sodium thiopental and 250 milligrams of...

  13. 21 CFR 522.2444b - Sodium thiopental, sodium pentobarbital for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium thiopental, sodium pentobarbital for... FORM NEW ANIMAL DRUGS § 522.2444b Sodium thiopental, sodium pentobarbital for injection. (a) Specifications. Each gram of the drug contains 750 milligrams of sodium thiopental and 250 milligrams of...

  14. Hypnosis, hypnotic suggestibility, memory, and involvement in films.

    PubMed

    Maxwell, Reed; Lynn, Steven Jay; Condon, Liam

    2015-05-01

    Our research extends studies that have examined the relation between hypnotic suggestibility and experiential involvement and the role of an hypnotic induction in enhancing experiential involvement (e.g., absorption) in engaging tasks. Researchers have reported increased involvement in reading (Baum & Lynn, 1981) and music-listening (Snodgrass & Lynn, 1989) tasks during hypnosis. We predicted a similar effect for film viewing: greater experiential involvement in an emotional (The Champ) versus a non-emotional (Scenes of Toronto) film. We tested 121 participants who completed measures of absorption and trait dissociation and the Harvard Group Scale of Hypnotic Susceptibility and then viewed the two films after either an hypnotic induction or a non-hypnotic task (i.e., anagrams). Experiential involvement varied as a function of hypnotic suggestibility and film clip. Highly suggestible participants reported more state depersonalization than less suggestible participants, and depersonalization was associated with negative affect; however, we observed no significant correlation between hypnotic suggestibility and trait dissociation. Although hypnosis had no effect on memory commission or omission errors, contrary to the hypothesis that hypnosis facilitates absorption in emotionally engaging tasks, the emotional film was associated with more commission and omission errors compared with the non-emotional film. PMID:25594911

  15. Cross-evidence for hypnotic susceptibility through nonlinear measures on EEGs of non-hypnotized subjects

    PubMed Central

    Chiarucci, Riccardo; Madeo, Dario; Loffredo, Maria I.; Castellani, Eleonora; Santarcangelo, Enrica L.; Mocenni, Chiara

    2014-01-01

    Assessment of hypnotic susceptibility is usually obtained through the application of psychological instruments. A satisfying classification obtained through quantitative measures is still missing, although it would be very useful for both diagnostic and clinical purposes. Aiming at investigating the relationship between the cortical brain activity and the hypnotic susceptibility level, we propose the combined use of two methodologies - Recurrence Quantification Analysis and Detrended Fluctuation Analysis - both inherited from nonlinear dynamics. Indicators obtained through the application of these techniques to EEG signals of individuals in their ordinary state of consciousness allowed us to obtain a clear discrimination between subjects with high and low susceptibility to hypnosis. Finally a neural network approach was used to perform classification analysis. PMID:25002038

  16. Cross-evidence for hypnotic susceptibility through nonlinear measures on EEGs of non-hypnotized subjects

    NASA Astrophysics Data System (ADS)

    Chiarucci, Riccardo; Madeo, Dario; Loffredo, Maria I.; Castellani, Eleonora; Santarcangelo, Enrica L.; Mocenni, Chiara

    2014-07-01

    Assessment of hypnotic susceptibility is usually obtained through the application of psychological instruments. A satisfying classification obtained through quantitative measures is still missing, although it would be very useful for both diagnostic and clinical purposes. Aiming at investigating the relationship between the cortical brain activity and the hypnotic susceptibility level, we propose the combined use of two methodologies - Recurrence Quantification Analysis and Detrended Fluctuation Analysis - both inherited from nonlinear dynamics. Indicators obtained through the application of these techniques to EEG signals of individuals in their ordinary state of consciousness allowed us to obtain a clear discrimination between subjects with high and low susceptibility to hypnosis. Finally a neural network approach was used to perform classification analysis.

  17. Hypnotics' association with mortality or cancer: a matched cohort study

    PubMed Central

    Langer, Robert D; Kline, Lawrence E

    2012-01-01

    Objectives An estimated 6%–10% of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality. Setting A large integrated health system in the USA. Design Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis. Subjects Subjects (mean age 54 years) were 10 529 patients who received hypnotic prescriptions and 23 676 matched controls with no hypnotic prescriptions, followed for an average of 2.5 years between January 2002 and January 2007. Main outcome measures Data were adjusted for age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer. Hazard ratios (HRs) for death were computed from Cox proportional hazards models controlled for risk factors and using up to 116 strata, which exactly matched cases and controls by 12 classes of comorbidity. Results As predicted, patients prescribed any hypnotic had substantially elevated hazards of dying compared to those prescribed no hypnotics. For groups prescribed 0.4–18, 18–132 and >132 doses/year, HRs (95% CIs) were 3.60 (2.92 to 4.44), 4.43 (3.67 to 5.36) and 5.32 (4.50 to 6.30), respectively, demonstrating a dose–response association. HRs were elevated in separate analyses for several common hypnotics, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates and sedative antihistamines. Hypnotic use in the upper third was associated with a significant elevation of incident cancer; HR=1.35 (95% CI 1.18 to 1.55). Results were robust within groups suffering each comorbidity, indicating that the death and cancer hazards associated with hypnotic drugs were not attributable to pre-existing disease. Conclusions Receiving hypnotic prescriptions was associated with greater than threefold increased hazards of death even when prescribed <18 pills/year. This association held in separate analyses for several commonly used

  18. Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

    PubMed Central

    Moniruzzaman, Md.; Atikur Rahman, Md.; Ferdous, Afia

    2015-01-01

    Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties. PMID:25861372

  19. [Hypnotic communication and hypnosis in clinical practice].

    PubMed

    Wehrli, Hans

    2014-07-01

    In addition to usual medical care it is often critical to consider the patient's inner world in order to sensitively differentiate between harmful and helpful suggestive elements. The respective abilities in terms of hypnotic communication can be easily learned. Confident, empathic attention and a calm, understanding and figurative language narrowing the focus on positive emotions and positive change, which have been shown to improve the patient's chances of healing, are of particular importance. Proper clinical hypnosis goes one step further: it makes explicit use of suggestions, trance, and trance phenomena. The major clinical indications for hypnosis include psychosomatic disorders, anxiety disorders, obsessive-compulsive disorders, depression, and pain syndromes. Hypnosis can also be employed as an adjunct for surgical therapy. PMID:24985229

  20. Confusion and hypnotics in demented patients

    PubMed Central

    Mead, M. G.; Castleden, C. M.

    1982-01-01

    Eleven elderly confused patients were given a single dose of chlormethiazole, temazepam and placebo on separate nights with-in a 10-day period. There was no statistically significant difference between the three treatments the next morning in any of the tests, which included subjective and objective measures of mental ability, orientation and hangover effect. These results mirror those previously found in normal, healthy, elderly patients, and do not therefore support the contention that hypnotics increase confusion in demented patients, or that such patients are more sensitive to their actions. Indeed, plasma drug concentrations were on average twice as high in demented as in normal elderly subjects, thus raising the possibility of decreased sensitivity in the demented group. There was little correlation between plasma concentration and pharmacological effect. PMID:6130151

  1. Terahertz spectroscopic study of benzodiazepine sedative hypnotics

    NASA Astrophysics Data System (ADS)

    Deng, Fusheng; Shen, Jingling; Wang, Xianfeng

    2011-08-01

    Terahertz time domain spectroscopy (THz-TDS) is used to the pure active ingredient of three benzodiazepine sedative hypnotics with similar molecular structure. The absorption spectra of them are studied in the range of 0.2~2.6THz. Based on the experiment, the theoretical simulation results of diazepam, nitrazepam and clonazepam are got by the Gaussian03 package of DFT/B3LYP/6-31G* method in single-molecule models. The experimental results show that even if the molecular structure and medicine property of them are similar, the accurate identification of them can still be done with their characteristic absorption spectra. Theoretical simulation results are well consistent with the experimental results. It demonstrates that absorption peaks of them in THz range mainly come from intra-molecular forces and are less affected by the intermolecular interaction and crystal effects.ô

  2. Hypnotic hypermnesia: the empty set of hypermnesia.

    PubMed

    Erdelyi, M H

    1994-10-01

    Although a long tradition exists suggesting that hypnosis can enhance memory (hypnotic hypermnesia), the experimental literature is quite mixed. When, however, laboratory studies are classified according to the type of stimulus and memory tests employed, a remarkable orderliness of outcomes emerges: Recall tests for high-sense stimuli (e.g., poetry, meaningful pictures) almost always produce hypermnesia, but not recognition tests for low-sense stimuli (e.g., nonsense syllables, word lists). An important methodological issue is whether the recall increments for high-sense stimuli constitute enhanced memory or enhanced reporting (laxer response criteria). Recent laboratory literatures show that, beyond response criterion effects, true memory enhancement (hypermnesia) exists. Experiments conducted over the past decade, however, demonstrate that it is repeated retrieval effort and not hypnosis that is responsible for hypermnesia: Repeated testing without hypnosis yields as much hypermnesia as with hypnosis. PMID:7960293

  3. Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice.

    PubMed

    Hong, Sa-Ik; Kwon, Seung-Hwan; Hwang, Ji-Young; Ma, Shi-Xun; Seo, Jee-Yeon; Ko, Yong-Hyun; Kim, Hyoung-Chun; Lee, Seok-Yong; Jang, Choon-Gon

    2016-03-01

    Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantl. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findingssuggest that modulation of D2-like receptors might enhance the effect of MT on sleep. PMID:26902082

  4. Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice

    PubMed Central

    Hong, Sa-Ik; Kwon, Seung-Hwan; Hwang, Ji-Young; Ma, Shi-Xun; Seo, Jee-Yeon; Ko, Yong-Hyun; Kim, Hyoung-Chun; Lee, Seok-Yong; Jang, Choon-Gon

    2016-01-01

    Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep. PMID:26902082

  5. The role of expectancy in hypnotic hypermnesia: a brief communication.

    PubMed

    Grabowski, K L; Roese, N J; Thomas, M R

    1991-10-01

    Previous research has yielded equivocal evidence of hypnotic memory enhancement. The present experiment assessed the effects of expectancy and hypnotizability on recall for videotaped material under waking and hypnotic conditions. Ss (N = 138) were informed of hypnotic induction either before (expectancy condition) or after (no expectancy condition) watching a videotaped enactment of a crime and completing an initial waking recall test (RI). Both groups then underwent hypnotic induction, and completed the test again (R2). Ss' raw recall scores were significantly greater under hypnotic than waking conditions, but this hypermnesia was not evident when scores were corrected for mere increase in rate of responding. Ss expecting later hypnosis scored significantly higher than Ss with no such expectations, but again, this difference was not evident in corrected scores. Hypnotizability of Ss was, however, related to corrected recall, with high hypnotizable Ss displaying the greatest increase in rate of responding from R1 to R2. No evidence for the hypothesized "suppression effect" underlying hypnotic hypermnesia was found. PMID:1937989

  6. Inhaled toluene produces pentobarbital-like discriminative stimulus effects in mice

    SciTech Connect

    Rees, D.C.; Coggeshall, E.; Balster, R.L.

    1985-10-07

    The abuse of volatile solvents may be due to their ability to produce an intoxication similar to that produced by classical central nervous system depressants such as the barbiturates and ethanol. To evaluate this hypothesis, mice were trained to discriminate pentobarbital from saline injections in a two-lever operant task. Stimulus generalization was examined following 20-min inhalation exposures to toluene (300-5400 ppm). In 8 of 10 subjects, pentobarbital-lever responding occurred following toluene exposure indicating an overlap in the discriminative stimulus properties of toluene and pentobarbital.

  7. Age-dependent inhibition of pentobarbital sleeping time by ozone in mice and rats

    SciTech Connect

    Canada, A.T.; Calabrese, E.J.; Leonard, D.

    1986-09-01

    The effect of age on the metabolism of pentobarbital in mice and rats was investigated following exposure to 0.3 ppm of ozone for 3.75 hr. Young animals were 2.5 months of age and the mature were 18 months. The pentobarbital sleeping time was significantly prolonged following the ozone exposure in both the mice and rats when compared with an air control. No ozone effect on sleeping time was found in the young animals. The results indicate that there may be an age-related sensitivity to the occurrence of ozone-related inhibition of pentobarbital metabolism.

  8. Therapy of vaginismus by hypnotic desensitization.

    PubMed

    Fuchs, K

    1980-05-01

    Fear and anxiety are of tremendous importance in the production and maintenance of a symptom. Vaginismus, as a reaction of avoidance of an anxiety-producing situation, is readily amenable to treatment by systematic desensitization. This may proceed mainly in two ways: "in vitro" or "in vivo." In order to strengthen and speed up the densensitization process, we used hypnotic techniques in a dynamic approach. The "in vitro" treatment proceeds with imagery, under hypnosis, of an "anxiety hierarchy" of increasingly erotic and sexually intimate situations which will be reproduced at home with the partner, until sexual intercourse is achieved. In the "in vivo" method the patient learns self-hypnosis and then inserts in the vagina first a finger, and then Hegar dilators of gradually increasing sizes. The partner, the patient, and the physician will then successively proceed to insertion, forming a team-referred work situation. This continues until the "female superior position," practiced first with the largest dilator, is reproduced at home by intercourse. Between 1965 and 1974 we treated 71 women with this method. Good results were obtained in 16 of 18 by the "in vitro" technique and in 53 of 54 by the "in vivo" technique. One patient was referred from the "in vitro" group to the "in vivo" group. In follow-up of 2 to 5 years there was no relapse or symptom substitution. PMID:6102843

  9. Is suvorexant a better choice than alternative hypnotics?

    PubMed

    Kripke, Daniel F

    2015-01-01

    Suvorexant is a novel dual orexin receptor antagonist (DORA) newly introduced in the U.S. as a hypnotic, but no claim of superiority over other hypnotics has been offered.  The manufacturer argued that the 5 and 10 mg starting doses recommended by the FDA might be ineffective.  The manufacturer's main Phase III trials had not even included the 10 mg dosage, and the 5 mg dosage had not been tested at all in registered clinical trials at the time of approval.  Popular alternative hypnotics may be similarly ineffective, since the FDA has also reduced the recommended doses for zolpidem and eszopiclone.  The "not to exceed" suvorexant dosage of 20 mg does slightly increase sleep.  Because of slow absorption, suvorexant has little effect on latency to sleep onset but some small effect in suppressing wakening after sleep onset and in improving sleep efficiency. The FDA would not approve the manufacturer's preferred 40 mg suvorexant dosage, because of concern with daytime somnolence, driving impairment, and possible narcolepsy-like symptoms.  In its immediate benefits-to-risks ratio, suvorexant is unlikely to prove superior to currently available hypnotics-possibly worse-so there is little reason to prefer over the alternatives this likely more expensive hypnotic less-tested in practice.  Associations are being increasingly documented relating hypnotic usage with incident cancer, with dementia risks, and with premature death.  There is some basis to speculate that suvorexant might be safer than alternative hypnotics in terms of cancer, dementia, infections, and mortality.  These safety considerations will remain unproven speculations unless adequate long-term trials can be done that demonstrate suvorexant advantages. PMID:26594338

  10. Effects of pentobarbital on plasma glucose and free fatty acids in the rat.

    NASA Technical Reports Server (NTRS)

    Furner, R. L.; Neville, E. D.; Talarico, K. S.; Feller, D. D.

    1972-01-01

    Hyperglycemia and hypolipemia were observed in rats after the injection of sodium pentobarbital. The observed changes were independent of whether the blood was collected by decapitation or by needle puncture of the aorta. The hyperglycemic response was caused by two factors including the stress of the injection per se and the pharmacological action of the drug. Hyperlipemia was observed at 5 min postinjection. However, pentobarbital decreased plasma free fatty acids by 15 min postinjection. Both the hyperglycemia and hypolipemia responses were dose dependent.

  11. The existence of a hypnotic state revealed by eye movements.

    PubMed

    Kallio, Sakari; Hyönä, Jukka; Revonsuo, Antti; Sikka, Pilleriin; Nummenmaa, Lauri

    2011-01-01

    Hypnosis has had a long and controversial history in psychology, psychiatry and neurology, but the basic nature of hypnotic phenomena still remains unclear. Different theoretical approaches disagree as to whether or not hypnosis may involve an altered mental state. So far, a hypnotic state has never been convincingly demonstrated, if the criteria for the state are that it involves some objectively measurable and replicable behavioural or physiological phenomena that cannot be faked or simulated by non-hypnotized control subjects. We present a detailed case study of a highly hypnotizable subject who reliably shows a range of changes in both automatic and volitional eye movements when given a hypnotic induction. These changes correspond well with the phenomenon referred to as the "trance stare" in the hypnosis literature. Our results show that this 'trance stare' is associated with large and objective changes in the optokinetic reflex, the pupillary reflex and programming a saccade to a single target. Control subjects could not imitate these changes voluntarily. For the majority of people, hypnotic induction brings about states resembling normal focused attention or mental imagery. Our data nevertheless highlight that in some cases hypnosis may involve a special state, which qualitatively differs from the normal state of consciousness. PMID:22039474

  12. Reversible analgesia, atonia, and loss of consciousness on bilateral intracerebral microinjection of pentobarbital.

    PubMed

    Devor, M; Zalkind, V

    2001-10-01

    Concussion, asphyxia, and systemically administered general anesthetics all induce reversible depression of the organism's response to noxious stimuli as one of the elements of loss of consciousness. This is so even for barbiturate anesthetics, which have only modest analgesic efficacy at subanesthetic doses. Little is known about the neural circuits involved in this form of antinociception, although for anesthetic agents, at least, it is usually presumed that the drugs act in widely distributed regions of the nervous system. We now report the discovery of a focal zone in the brainstem mesopontine tegmentum in rats at which microinjection of minute quantities of pentobarbital induces a transient, reversible anesthetic-like state with non-responsiveness to noxious stimuli, flaccid atonia, and absence of the righting reflex. The behavioral suppression is accompanied by slow-wave EEG and, presumably, loss of consciousness. This zone, which we refer to as the mesopontine tegmental anesthesia locus (MPTA), apparently contains a barbiturate-sensitive 'switch' for both cortical and spinal activity. The very existence of the MPTA locus has implications for an understanding of the neural circuits that control motor functions and pain sensation, and for the cerebral representation of consciousness. PMID:11576749

  13. Imagery vividness, hypnotic susceptibility, and the perception of fragmented stimuli.

    PubMed

    Wallace, B

    1990-02-01

    Two experiments were conducted to determine the role of hypnotic susceptibility level (high or low) and imaging ability (vivid or poor) in the performance of gestalt closure tasks. In Experiment 1, subjects were required to identify fragmented stimuli in the Closure Speed Test and in the Street Test. In Experiment 2, subjects reported on fragmented stimuli that were projected to the right eye and subsequently produced an afterimage. Individuals were asked to identify the composite if possible and to report on the duration of the afterimage. In both experiments, hypnotic susceptibility level and imaging ability affected reports of gestalt closure. The greatest number of correct closures was reported by those who were both high in hypnotic susceptibility and vivid in imaging ability. In addition, in the second experiment, this group also reported the longest enduring afterimage. These results are discussed in terms of the processes required to perform in a gestalt closure task. PMID:2319447

  14. Is suvorexant a better choice than alternative hypnotics?

    PubMed Central

    Kripke, Daniel F.

    2015-01-01

    Suvorexant is a novel dual orexin receptor antagonist (DORA) newly introduced in the U.S. as a hypnotic, but no claim of superiority over other hypnotics has been offered.  The manufacturer argued that the 5 and 10 mg starting doses recommended by the FDA might be ineffective.  The manufacturer's main Phase III trials had not even included the 10 mg dosage, and the 5 mg dosage had not been tested at all in registered clinical trials at the time of approval.  Popular alternative hypnotics may be similarly ineffective, since the FDA has also reduced the recommended doses for zolpidem and eszopiclone.  The "not to exceed" suvorexant dosage of 20 mg does slightly increase sleep.  Because of slow absorption, suvorexant has little effect on latency to sleep onset but some small effect in suppressing wakening after sleep onset and in improving sleep efficiency. The FDA would not approve the manufacturer's preferred 40 mg suvorexant dosage, because of concern with daytime somnolence, driving impairment, and possible narcolepsy-like symptoms.  In its immediate benefits-to-risks ratio, suvorexant is unlikely to prove superior to currently available hypnotics—possibly worse—so there is little reason to prefer over the alternatives this likely more expensive hypnotic less-tested in practice.  Associations are being increasingly documented relating hypnotic usage with incident cancer, with dementia risks, and with premature death.  There is some basis to speculate that suvorexant might be safer than alternative hypnotics in terms of cancer, dementia, infections, and mortality.  These safety considerations will remain unproven speculations unless adequate long-term trials can be done that demonstrate suvorexant advantages. PMID:26594338

  15. Hypnotic, anticonvulsant and anxiolytic effects of 1-nitro-2-phenylethane isolated from the essential oil of Dennettia tripetala in mice.

    PubMed

    Oyemitan, Idris Ajayi; Elusiyan, Christianah Abimbola; Akanmu, Moses Atanda; Olugbade, Tiwalade Adewale

    2013-11-15

    This study investigated the hypnotic, anti-convulsant and anxiolytic effects of 1-nitro-2-phenylethane (BPNE) obtained from the oil of Dennettia tripetala G. Baker (Annonaceae) and established its mechanism of action. The essential oil (EO) from the leaf, fruit and seed was obtained by hydrodistillation, followed by isolation of BPNE purified to 99.2% by accelerated gradient chromatography on silica, and identified by NMR and GC-MS. The pure BPNE and EO of the dried seed (93.6%) were comparatively evaluated for hypnotic, anticonvulsant and anxiolytic effects in mice. The acute toxicity of BPNE was determined and the LD50 was 490 mg/kg, intrapritonealy. The hypnotic activities of the EO and BPNE (50-400 mg/kg, i.p.) were assessed by loss of righting reflex, while sodium pentobarbitone (PBS) and diazepam (DZM) were used as positive controls. The anticonvulsant and anxiolytic effects of the EO and BPNE were evaluated in mice. Both BPNE and EO at doses ≥100 mg/kg induced spontaneous hypnosis with loss of righting reflex, significantly decreased sleep latency (SL) and also increased total sleeping time (TST) dose-dependently. They had comparable activity with NAP in TST. The BPNE exhibited higher hypnotic potency than EO at the same dose levels. The EO and BPNE offered comparable dose-related protections against PTZ- and strychnine-induced convulsions. Flumazenil (2 mg/kg) blocked the hypnotic and anticonvulsant (PTZ-convulsions) effects of both EO and BPNE. The essential oil at 5-20 mg/kg dose levels significantly (p<0.05) increased the percentage time spent and number of entries into the open arms. While at the same dose range BPNE significantly (p<0.05) increased the percentage time spent and the number of entries into the open arms respectively. The study concluded that 1-nitro-2-phenylethane exhibited dose dependent significant hypnotic, anticonvulsant and anxiolytic effects and it is the compound largely responsible for the neuropharmacological effects of the

  16. Hypnotic treatment of Sleep Terror Disorder: a case report.

    PubMed

    Koe, G G

    1989-07-01

    This case report describes the hypnotic treatment of Sleep Terror Disorder in a 16-year-old male who was resistant to other forms of treatment. In this patient, night terrors seemed to be precipitated by nocturnal noises wakening him from deep sleep. Posthypnotic suggestions reducing awareness of nocturnal sensory stimulation successfully eliminated his night terrors. PMID:2773819

  17. Hypnotic Susceptibility and Personality as Measured by the MMPI-2.

    ERIC Educational Resources Information Center

    Parker, Wayne D.

    This study evaluated personality variables that underlie hypnotic susceptibility. It was correlational, did not require ongoing contact with participants, and included a validation study as an integral component. The subjects were 359 college students (250 in the original sample and 109 in the cross validation study) taking undergraduate courses…

  18. Pharmacological evaluation of Mallotus philippinensis (Lam.) Muell.-Arg. fruit hair extract for anti-inflammatory, analgesic and hypnotic activity

    PubMed Central

    Gangwar, Mayank; Gautam, Manish Kumar; Ghildiyal, Shivani; Nath, Gopal; Goel, Raj Kumar

    2016-01-01

    Objective: Recently, we observed wound healing activity of 50% ethanol extract of Mallotus philippinensis Muell. Arg (MP) fruit hairs extract (MPE). In several intestinal infections, localized inflammation is of common occurrence and hence we evaluated the anti-inflammatory, analgesic and hypnotic activity of MPE in different rat experimental models. Materials and Methods: Anti-inflammatory activity was evaluated by carrageenan (acute) and turpentine oil induced formalin (subacute) induced paw edema and while granuloma pouch (subacute) in rats. Analgesic and hypnotic activity of MPE was undertaken by tail-flick, hot-plate, and acetic acid-induced writhing tests while pentobarbitone-induced hypnotic potentiation in rats. Results: MPE at a dose of 200 mg/kg at 3 h after their administration showed inhibition of formalin-induced paw edema by 41.60% (P < 0.001) and carrageenan-induced paw edema by 55.30% (P < 0.001). After 7 days of treatments, MPE showed 38.0% (P < 0.001) inhibition against formalin-induced paw edema and reduced weight of turpentine-induced granuloma pouch by 29.6% (P < 0.01) and volume of exudates by 26.1% (P < 0.01), respectively. MPE (200 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 120 min as evidenced by increased latency period in tail flick method and increased reaction time in the hot-plate test while the reduction in the number of acetic acid-induced writhes by 45.7% (P < 0.001). The pentobarbitone-induced hypnosis model showed potentiation, as defined by increased duration of sleep in treated group rats as compared to control. Conclusion: Thus, the study revealed MPE is effective in reducing acute and subacute inflammation and showed effective and similar analgesic activity. This seemed to be safe in the treatment of pain and inflammation. PMID:27069718

  19. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system.

    PubMed

    Bixler, E O; Kales, A; Brubaker, B H; Kales, J D

    1987-01-01

    The rates of reported adverse drug reactions involving the central nervous system were compared among patients taking any of three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. These rates, based upon data collected through the spontaneous reporting system of the Food and Drug Administration, were controlled for the number and size of new prescriptions for each drug. In general, triazolam had much higher overall rates than did the other two drugs. Hyperexcitability and withdrawal effects were greatest for triazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates for other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs. Finally, daytime sedation was reported slightly more for flurazepam than triazolam and least for temazepam which was also reported most frequently as lacking hypnotic effect. PMID:2892212

  20. Neuro-Hypnotism: Prospects for Hypnosis and Neuroscience

    PubMed Central

    Kihlstrom, John F.

    2012-01-01

    The neurophysiological substrates of hypnosis have been subject to speculation since the phenomenon got its name. Until recently, much of this research has been geared toward understanding hypnosis itself, including the biological bases of individual differences in hypnotizability, state-dependent changes in cortical activity occurring with the induction of hypnosis, and the neural correlates of response to particular hypnotic suggestions (especially the clinically useful hypnotic analgesia). More recently, hypnosis has begun to be employed as a method for manipulating subjects' mental states, both cognitive and affective, to provide information about the neural substrates of experience, thought, and action. This instrumental use of hypnosis is particularly well-suited for identifying the neural correlates of conscious and unconscious perception and memory, and of voluntary and involuntary action. PMID:22748566

  1. Psychological Treatment of Insomnia in Hypnotic-Dependant Older Adults

    PubMed Central

    Soeffing, James P.; Lichstein, Kenneth L.; Nau, Sidney D.; McCrae, Christina S.; Wilson, Nancy M.; Aguillard, R. Neal; Lester, Kristin W.; Bush, Andrew J.

    2008-01-01

    Background The existing literature does not address the question of whether cognitive-behavioral therapy would have an impact on insomnia in older adults who are chronic users of sleep medication and have current insomnia, but are also stable in their quantity of medication usage during treatment. The present report seeks to answer this question. Methods Hypnotic-dependant older adults, who were stable in their amount of medication usage and still met the criteria for chronic insomnia put forth by American Academy of Sleep Medicine, were treated using a cognitive-behavioral intervention for insomnia. The three-component treatment included relaxation training, stimulus control, and sleep hygiene instructions. Participants were randomly assigned to either the active treatment group or a comparably credible placebo control group, and were instructed not to alter their pattern of hypnotic consumption during treatment. Results The active treatment group had significantly better self-report measures of sleep at post-treatment. Statistically significant improvement was paralleled by clinically meaningful improvement for key sleep variables. As planned, there was no significant change in sleep medication usage from pre- to post-treatment. Conclusions The findings support the use of cognitive-behavioral therapy for insomnia in hypnotic-dependant older adults. PMID:17644419

  2. A cross-validation of two differing measures of hypnotic depth.

    PubMed

    Pekala, Ronald J; Maurer, Ronald L

    2013-01-01

    Several sets of regression analyses were completed, attempting to predict 2 measures of hypnotic depth: the self-reported hypnotic depth score and hypnoidal state score from variables of the Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure (PCI-HAP). When attempting to predict self-reported hypnotic depth, an R of .78 with Study 1 participants shrank to an r of .72 with Study 2 participants, suggesting mild shrinkage for this more attributional measure of hypnotic depth. Attempting to predict hypnoidal state (an estimate of trance) using the same procedure, yielded an R of .56, that upon cross-validation shrank to an r of .48. These and other results suggest that, although there is some variance in common, the self-reported hypnotic depth score appears to be tapping a different construct from the hypnoidal state score. PMID:23153387

  3. DIFFERENTIAL IMPACT OF HYPOTHERMIA AND PENTOBARBITAL ON BRAINSTEM AUDITORY EVOKED RESPONSE

    EPA Science Inventory

    Two experiments were conducted to determine the effects of hypothermia and pentobarbital anesthesia, alone and in combination, on the brainstem auditory evoked responses (BAERs) of rats. n experiment I, unanesthetized rats were cooled to colonic temperatures 0.5 and 1.0 degrees C...

  4. Stability-Indicating Assay for the Determination of Pentobarbital Sodium in Liquid Formulations.

    PubMed

    Ajemni, Myriam; Balde, Issa-Bella; Kabiche, Sofiane; Carret, Sandra; Fontan, Jean-Eudes; Cisternino, Salvatore; Schlatter, Joël

    2015-01-01

    A stability-indicating assay by reversed-phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of pentobarbital sodium in oral formulations: a drug used for infant sedation in computed tomography (CT) or magnetic resonance imaging (MRI) scan. The chromatographic separation was achieved on a reversed-phase C18 column, using isocratic elution and a detector set at 214 nm. The optimized mobile phase consisted of a 0.01 M potassium buffer pH 3 and methanol (40 : 60, v/v). The flow rate was 1.0 mL/min and the run time of analysis was 5 min. The linearity of the method was demonstrated in the range of 5 to 250 μg/mL pentobarbital sodium solution (r (2) = 0.999). The limit of detection and limit of quantification were 2.10 and 3.97 μg/mL, respectively. The intraday and interday precisions were less than 2.1%. Accuracy of the method ranged from 99.2 to 101.3%. Stability studies indicate that the drug is stable to sunlight and in aqueous solution. Accelerated pentobarbital sodium breakdown by strong alkaline, acidic, or oxidative stress produced noninterfering peaks. This method allows accurate and reliable determination of pentobarbital sodium for drug stability assay in pharmaceutical studies. PMID:26543481

  5. Anxiolytic, sedative, and hypnotic activities of aqueous extract of Morinda citrifolia fruit.

    PubMed

    Kannan, Sridharan; Manickam, Shanti; RajaMohammed, Meher Ali

    2014-04-01

    Morinda citrifolia (Indian mulberry or noni) fruit has been long used as a folk medicine for a wide range of health purposes as it is claimed to have analgesic, antiinflammatory, antioxidant, detoxifier, and cell-rejuvenator properties. A recent study has revealed central nervous system suppressant nature of its extract. Hence, the present study has evaluated the anxiolytic, sedative, and hypnotic effects of the aqueous extracts of Morinda citrifolia in rodents in comparison to diazepam. Anxiety was assessed by 'Isolation-induced aggression' model, sedation by 'Spontaneous locomotor activity using actophotometer' and hypnotic activity by 'Prolongation of ketamine-induced sleeping time'. Six male mice were used for each of the groups and postdose, all the six that received diazepam had shown an inhibition of aggression, whereas in the test group, five of six mice and none in the control group had shown an inhibition of aggression (P = 0.0007). Similarly, for the sedative activity, the total number of spontaneous locomotor activity at 30 min following drug administration was found to be 364.67 ± 10.74, 123.16 ± 8.33, and 196.67 ± 3.7, while at 60 min it was found to be 209 ± 12.98, 49 ± 5.78, and 92 ± 2.5 (mean ± SD) for the control, standard, and test groups of mice respectively (P < 0.001). Hypnotic activity was measured by prolongation of ketamine-induced sleeping time wherein the onset and duration of loss of righting reflex were compared among each group of mice. The time in minutes for the onset in control, standard, and test groups was 4.01 ± 0.22, 1.23 ± 0.05, and 2.23 ± 0.07, respectively. The duration of loss of righting reflex was 44.23 ± 0.59, 56.03 ± 1.34, and 50.57 ± 0.36, respectively. Both these were statistically significant (P < 0.001). However, more clinical studies are needed to assess the long-term effects of the extract in humans. PMID:24948855

  6. Further Investigation of the Relationship between Hypnotic Susceptibility and Classroom Seating.

    ERIC Educational Resources Information Center

    Stam, Henderikus J.; And Others

    1981-01-01

    In an attempt to replicate the finds of Sackeim, Paulhus, and Weiman (1979), three classrooms of college students were tested for hypnotic susceptibility, handedness, and seating preferences. No relationships between variables were found for males. For females, relationships were inconsistent. Relationships between hypnotic susceptibility and…

  7. Mediation and Moderation of Psychological Pain Treatments: Response Expectancies and Hypnotic Suggestibility

    ERIC Educational Resources Information Center

    Milling, Leonard S.; Reardon, John M.; Carosella, Gina M.

    2006-01-01

    The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction,…

  8. The Computer-Assisted Hypnosis Scale: Standardization and Norming of a Computer-Administered Measure of Hypnotic Ability.

    ERIC Educational Resources Information Center

    Grant, Carolyn D.; Nash, Michael R.

    1995-01-01

    In a counterbalanced, within subjects, repeated measures design, 130 undergraduates were administered the Computer-Assisted Hypnosis Scale (CAHS) and the Stanford Hypnotic Susceptibility Scale and were hypnotized. The CAHS was shown to be a psychometrically sound instrument for measuring hypnotic ability. (SLD)

  9. The effects of conditioning with amphetamine on the thermic effects of amphetamine and pentobarbital.

    PubMed

    Hinson, R E; Streather, A; Cosburn, G

    1991-01-01

    1. Rats were injected with amphetamine (1.5 mg/kg) in the presence of a distinctive set of environmental stimuli (CS1) and saline in the presence of a different set of environmental stimuli (CS2) on different days for a total of 10 amphetamine and 20 saline injections. 2. The hyperthermic effect of amphetamine first increased but then declined to levels seen during the very first drug administration. 3. Following the conditioning phase, half the rats were injected with amphetamine in CS1 and half in CS2. Although there was little thermic effect of amphetamine injected in CS1, there was pronounced hyperthermia following amphetamine in CS2. 4. Next, pentobarbital (30 mg/kg) was administered to half the rats in CS1 and half in CS2. The hypothermic effect of pentobarbital was attenuated in CS2. PMID:1763195

  10. Spatiotemporal Changes of Neuronal Responses in the Primary Somatosensory Cortex to Noxious Tail Stimulation in Awake and Pentobarbital-Anesthetized Rats.

    PubMed

    Kuo, Chung-Chih; Lee, Jye-Chang; Chiou, Ruei-Jen; Tsai, Meng-Li; Yen, Chen-Tung

    2015-10-31

    Primary somatosensory cortex (SI) is a key area in the processing of nociceptor inputs to our consciousness. To clarify the columnar and laminar organization of SI for pain processing, we compared spatiotemporal changes in neuronal activities of the primary sensorimotor cortex (SmI) of the rat in response to noxious laser heat stimulation applied to the mid-tail. Longitudinal and vertical array microelectrodes were chronically implanted in the cerebral cortex. Evoked neuronal activities, including intracortical local field potentials (LFP) and ensemble single-unit activity (SU) around SmI were simultaneously recorded. The effect of pentobarbital on the neuronal responses was evaluated in comparison with the neuronal responses in conscious animals to explore the potential substrate of nociceptive processing in the conscious state. The results from the experiment with longitudinal microelectrode arrays indicated that noxious stimulation induced a neuronal response which was spread widely around the SmI of the conscious rat, and the range of neuronal responses was limited to the tail region of the SmI under anesthesia. The results from the experiment with vertical microelectrode arrays showed the universal neuronal responses through all cortical layers of the SmI in conscious rats, and sodium pentobarbital suppressed these neuronal responses in the supragranular layers significantly relative to the deeper layers and basal activity. These results imply that a wider range of cortical activation, both in the horizontal or vertical dimension, might be important for nociceptive processing in the conscious state. PMID:26387657

  11. Effects of droperidol, pentobarbital, and ketamine on myogenic transcranial magnetic motor-evoked responses in humans.

    PubMed

    Kalkman, C J; Drummond, J C; Patel, P M; Sano, T; Chesnut, R M

    1994-12-01

    Myogenic motor-evoked responses to transcranial magnetic stimulation of the motor cortex (tcmag-MERs) may become clinically useful for the noninvasive assessment of motor pathway conduction during surgery. However, application is hindered because most anesthetic regimens result in severe depression of tcmag-MER amplitudes. As part of our systematic attempts to identify anesthetic agents and supplements suitable for use during tcmag-MER recording, we studied the effect of bolus doses of pentobarbital (1.5 mg/kg), droperidol (0.07 mg/kg), or ketamine (1 mg/kg), administered intravenously, on compound muscle action potentials to transcranial magnetic stimulation in five healthy volunteers. The doses were chosen to be comparable with doses that might be suitable for supplementation of a nitrous oxide/opioid anesthetic technique. Droperidol administration resulted in sustained amplitude depression of both tibialis and adductor pollicis tc-MERs to 30 +/- 9% and 39 +/- 14% of baseline (P < 0.01). Tcmag-MER amplitude changes after pentobarbital were variable, ranging from no change to substantial amplitude depression (to 20% of baseline) in two subjects. In contrast, ketamine administration did not result in significant amplitude depression. In three subjects, tibialis anterior amplitude increased to 150 to 220% of control values in the first 10 minutes after ketamine. Onset latency was unchanged after any drug. These data indicate that tcmag-MERs are moderately depressed after droperidol and pentobarbital but well preserved after ketamine. Ketamine may be a more suitable supplement to opioid/nitrous oxide anesthesia than droperidol or pentobarbital. PMID:7885550

  12. Decreased sensitivity to the hypnotic effects of ethanol early in ontogeny.

    PubMed

    Silveri, M M; Spear, L P

    1998-05-01

    Sensitivity to the hypnotic effects of ethanol was examined in Sprague-Dawley male and female rats at 16, 26, 36, 46, 56, or 96 days postnatally. Following administration of 3.5, 4.0, 4.5, or 5.0 g/kg of a 17% v/v ethanol solution, sleep times were recorded and blood alcohol levels (BALs) and brain alcohol levels (BrALs) were measured upon awakening. In addition to examining ethanol sleep time during ontogeny, data were used to estimate acute tolerance (indexed by the slope of the linear regressions of waking BALs and BrALs as a function of dose) and initial brain sensitivity to ethanol (indexed by calculating the y-intercept from the linear regression of BrALs as a function of sleep time). The results showed a marked increase in sensitivity to ethanol hypnosis during ontogeny, with young animals exhibiting shorter ethanol-induced sleep times and high waking BALs and BrALs. This ontogenetic increase in ethanol sensitivity was associated with a developmental decline in acute tolerance, with acute tolerance being most pronounced at postnatal day (P) 16 and evident only up to P36. Initial sensitivity conversely increased with age, with P16 pups showing lower initial brain sensitivity to ethanol than at all other ages. Gender differences emerged in adulthood, with males sleeping significantly longer than females at P56 and P96. These findings suggest that the marked insensitivity of young animals to the hypnotic effects of ethanol is related to both pronounced acute tolerance, as well as reduced initial brain sensitivity to ethanol early in life. PMID:9622449

  13. Dose effect of pentobarbital sodium on control of breathing in cats.

    PubMed

    Siafakas, N M; Bonora, M; Duron, B; Gautier, H; Milic-Emili, J

    1983-11-01

    The dose effect of pentobarbital sodium on integrated ("moving time average") phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR. PMID:6643193

  14. Effect of ketamine, pentobarbital, and morphine on Tc-99m-DISIDA hepatobiliary kinetics

    SciTech Connect

    Durakovic, A.; Dubois, A.

    1985-05-01

    The purpose of this study was to evaluate hapatobiliary kinetics of Tc-99m-DISIDA in dogs after administration of anesthetic sedative or narcotic agents. Four groups of six male Beagle dogs were studied as a non-treated control group and after parenteral administration of ketamine (30 mg/kg IM), pentobarbital (25 mg/kg IV) or morphine (1 mg/kg IV). Each animal was injected with 4 mCi Tc-99m-DISIDA and hepatobiliary scintigraphic studies were obtained using a gamma camera with parallel hole multipurpose collimator and an A/sup 3/ MDS computer. The authors determined; peak activity of Tc-99m-DISIDA in the liver, visualization and peak activity of gallbladder, and intestinal visualization of Tc-99m-DISIDA. Total bilirubin, LDH, SGOT and SGPT were not modified significantly after any drug compared to control. The results showed that two commonly used anesthetics and sedatives (ketamine and pentobarbital) have dramatic and opposite effects on extrahepatic biliary kinetics. Furthermore, ketamine, but not pentobarbital, significantly accelerates intrahepatic biliary kinetics. Finally, as expected, morphine delayed extrahepatic biliary kinetics. Thus, studies of biliary kinetics should be interpreted with caution when measurements are made after administration of anesthetic, sedative or narcotic agents.

  15. Correction for Inhibition Leads to an Allosteric Co-Agonist Model for Pentobarbital Modulation and Activation of α1β3γ2L GABAA Receptors

    PubMed Central

    Ziemba, Alexis M.; Forman, Stuart A.

    2016-01-01

    Background Pentobarbital, like propofol and etomidate, produces important general anesthetic effects through GABAA receptors. Photolabeling also indicates that pentobarbital binds to some of the same sites where propofol and etomidate act. Quantitative allosteric co-agonist models for propofol and etomidate account for modulatory and agonist effects in GABAA receptors and have proven valuable in establishing drug site characteristics and for functional analysis of mutants. We therefore sought to establish an allosteric co-agonist model for pentobarbital activation and modulation of α1β3γ2L receptors, using a novel approach to first correct pentobarbital activation data for inhibitory effects in the same concentration range. Methods Using oocyte-expressed α1β3γ2L GABAA receptors and two-microelectrode voltage-clamp, we quantified modulation of GABA responses by a low pentobarbital concentration and direct effects of high pentobarbital concentrations, the latter displaying mixed agonist and inhibitory effects. We then isolated and quantified pentobarbital inhibition in activated receptors using a novel single-sweep “notch” approach, and used these results to correct steady-state direct activation for inhibition. Results Combining results for GABA modulation and corrected direct activation, we estimated receptor open probability and optimized parameters for a Monod-Wyman-Changeux allosteric co-agonist model. Inhibition by pentobarbital was consistent with two sites with IC50s near 1 mM, while co-agonist model parameters suggest two allosteric pentobarbital agonist sites characterized by KPB ≈ 5 mM and high efficacy. The results also indicate that pentobarbital may be a more efficacious agonist than GABA. Conclusions Our novel approach to quantifying both inhibitory and co-agonist effects of pentobarbital provides a basis for future structure-function analyses of GABAA receptor mutations in putative pentobarbital binding sites. PMID:27110714

  16. Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit.

    PubMed

    Kripke, Daniel F

    2016-01-01

    This is a review of hypnotic drug risks and benefits, reassessing and updating advice presented to the Commissioner of the Food and Drug Administration (United States FDA). Almost every month, new information appears about the risks of hypnotics (sleeping pills). This review includes new information on the growing USA overdose epidemic, eight new epidemiologic studies of hypnotics' mortality not available for previous compilations, and new emphasis on risks of short-term hypnotic prescription. The most important risks of hypnotics include excess mortality, especially overdose deaths, quiet deaths at night, infections, cancer, depression and suicide, automobile crashes, falls, and other accidents, and hypnotic-withdrawal insomnia. The short-term use of one-two prescriptions is associated with greater risk per dose than long-term use. Hypnotics are usually prescribed without approved indication, most often with specific contraindications, but even when indicated, there is little or no benefit. The recommended doses objectively increase sleep little if at all, daytime performance is often made worse, not better, and the lack of general health benefits is commonly misrepresented in advertising. Treatments such as the cognitive behavioral treatment of insomnia and bright light treatment of circadian rhythm disorders might offer safer and more effective alternative approaches to insomnia. PMID:27303633

  17. Hypnotics and mortality in an elderly general population: a 12-year prospective study

    PubMed Central

    2013-01-01

    Background Hypnotics are widely used by the elderly, and their impact on mortality remains controversial. The inconsistent findings could be due to methodological limitations, notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use, for example, insomnia symptoms and excessive daytime sleepiness, depression and anxiety. Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders and sleep complaints. Methods Analyses were carried out on 6,696 participants aged 65 years or older randomly recruited from three French cities and free of dementia at baseline. Adjusted Cox proportional hazards models with delayed entry, and age of the participants as the time scale, were used to determine the association between hypnotic use and 12-year survival. Results At baseline, 21.7% of the participants regularly used at least one hypnotic. During follow-up, 1,307 persons died, 480 from cancer and 344 from cardiovascular disease. Analyses adjusted for study center, age and gender showed a significantly greater risk of all-cause and cardiovascular-related mortality with hypnotics, particularly benzodiazepines, and this increased with the number of hypnotics used. None of these associations were significant in models adjusting for sociodemographic and lifestyle characteristics, chronic disorders including cardiovascular pathologies, sleep and psychiatric disorders. Results remained unchanged when duration of past hypnotic intake or persistent versus intermittent use during follow-up were taken into account. Conclusions When controlling for a large range of potential confounders, the risk of mortality was not significantly associated with hypnotic use regardless of the type and

  18. Prenatal ethanol exposure affects temperature responses of adult rats to pentobarbital and diazepam alone and in combination with ethanol.

    PubMed

    Taylor, A N; Branch, B J; Randolph, D; Hill, M A; Kokka, N

    1987-06-01

    Long-term effects of prenatal alcohol exposure on body temperature responses to pentobarbital and diazepam and to either drug in combination with ethanol were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet during the last 2 weeks of gestation. Adult offspring of pair-fed and chow-fed dams served as nutritional and normal controls, respectively. Pentobarbital (6.25-25.0 mg/kg) and diazepam (2.5-10.0 mg/kg) produced significantly greater dose-related hypothermic responses in females than males. Following either pentobarbital or diazepam administration female prenatally ethanol-exposed (E) rats responded with a greater fall in body temperature than the controls. Significantly greater hypothermia occurred in both male and female E rats than in controls when ethanol (1.5 g/kg) was administered together with pentobarbital or diazepam. However, the drug combinations did not produce additive effects on body temperature in any prenatal treatment group. Pentobarbital produced acute cross-tolerance to ethanol while diazepam potentiated ethanol's effect. These studies confirm and extend our previous findings of enhanced hypothermic responses to ethanol in adult rats exposed to ethanol in utero and indicate that maternal alcohol consumption produces long-term effects on the central thermoregulatory systems of offspring. PMID:3307489

  19. Gamma-hydroxybutyric acid as hypnotic. Clinical and pharmacokinetic evaluation of gamma-hydroxybutyric acid as hypnotic in man.

    PubMed

    Hoes, M J; Vree, T B; Guelen, P J

    1980-01-01

    Gamma-Hydroxybutyric acid (GOH) was administered to three groups of four patients in 50, 75 or 100 mg/kg dose respectively, and sleep effects were scored, by sleep observation and questionnaire; GOH plasma levels were determined at 75-100 mg/kg, saliva and urine excretion at 100 mg/kg. Sleep induction was rapid and irresistible, subjects awoke at plasma levels of 90 micrograms/ml; sleep scores were good for 75 mg/kg, excellent for 100 mg/kg, notably on mood. For 75 or 100 mg/kg GOH had virtually disappeared from the blood eight hours after intake; twelve hours after intake no more GOH was detectable in urine; no correlation between plasma- and saliva levels was found. Plasma levels for 100 mg/kg dose were not at an anaesthetic level. So, GOH is a safe and good hypnotic at 75 or 100 mg/kg in clinical use. PMID:7449723

  20. Hypnotic depth and response to suggestion under standardized conditions and during FMRI scanning.

    PubMed

    Oakley, David A; Deeley, Quinton; Halligan, Peter W

    2007-01-01

    Hypnosis is a potentially valuable cognitive tool for neuroimaging studies. However, understandable concern that Magnetic Resonance Imaging (MRI) in particular may adversely affect hypnotic procedures remains. Measurements of hypnotic depth and responsiveness to suggestions were taken using a standardized procedure that met all the requirements for functional MRI (fMRI). Testing outside the scanning environment showed reliable and stable changes in subjective hypnotic depth, with no carryover once the hypnosis had been terminated. Within-subject comparisons showed that the magnitude and pattern of these changes and the degree of responsiveness to hypnotic suggestion were not discernibly affected by the fMRI environment. It is concluded that hypnosis can be employed as a discrete and reliable cognitive tool within fMRI neuroimaging settings. PMID:17135062

  1. The Psychophysics of Cold Pressor Pain and Its Modification through Hypnotic Suggestion

    ERIC Educational Resources Information Center

    Hilgard, Ernest R.; And Others

    1974-01-01

    Earlier reports of the pain of putting hand and forearm in circulating ice water were recomputed to study how subjects scale that pain and to find appropriate measures of its reduction under hypnotic analgesia. (Editor)

  2. Hypnotic change in combat dreams of two veterans with posttraumatic stress disorder.

    PubMed

    Eichelman, B

    1985-01-01

    The recurrent nocturnal traumatic dreams of two veterans were dispelled with hypnosis. Dream substitutions were rehearsed in hypnotic trance and subsequently dreamed at night, and afterward the original traumatic dreams ceased. PMID:3966569

  3. Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

    PubMed Central

    Kripke, Daniel F.

    2016-01-01

    This is a review of hypnotic drug risks and benefits, reassessing and updating advice presented to the Commissioner of the Food and Drug Administration (United States FDA). Almost every month, new information appears about the risks of hypnotics (sleeping pills). This review includes new information on the growing USA overdose epidemic, eight new epidemiologic studies of hypnotics’ mortality not available for previous compilations, and new emphasis on risks of short-term hypnotic prescription. The most important risks of hypnotics include excess mortality, especially overdose deaths, quiet deaths at night, infections, cancer, depression and suicide, automobile crashes, falls, and other accidents, and hypnotic-withdrawal insomnia. The short-term use of one-two prescriptions is associated with greater risk per dose than long-term use. Hypnotics are usually prescribed without approved indication, most often with specific contraindications, but even when indicated, there is little or no benefit. The recommended doses objectively increase sleep little if at all, daytime performance is often made worse, not better, and the lack of general health benefits is commonly misrepresented in advertising. Treatments such as the cognitive behavioral treatment of insomnia and bright light treatment of circadian rhythm disorders might offer safer and more effective alternative approaches to insomnia. PMID:27303633

  4. Use of benzodiazepines, hypnotics, and anxiolytics in major depressive disorder: association with chronic pain diseases.

    PubMed

    Liu, Xianchen; Ye, Wenyu; Watson, Peter; Tepper, Ping

    2010-08-01

    We examined the use of benzodiazepines (BZD), hypnotics, and anxiolytics and their associations with chronic pain diseases (CPD) in patients with major depressive disorder (MDD). A retrospective analysis of 153,913 MDD patients (18-64 years) in a large administrative insured claims database during the year 2006 was performed. Results showed that during the study year, 33.1% of the patients had been prescribed BZD; 16.9%, hypnotics; and 6.1%, anxiolytics. The use of BZD and hypnotics increased with age. Patients with CPD were more likely than those without CPD to use BZD (41.2% vs. 27.0%, p < 0.001), hypnotics (21.7% vs. 13.3%, p < 0.001), and anxiolytics (7.8% vs. 4.8%, p < 0.01). After adjustment for demographics and comorbidities, CPD was still significantly associated with increased use of BZD (OR = 1.62), hypnotics (OR = 1.49), and anxiolytics (OR = 1.51). Further research is needed to examine the long-term benefits and risks of BZD and hypnotics in the treatment of MDD and CPD. PMID:20699718

  5. Activation of alpha6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA.

    PubMed

    Fisher, Matthew T; Fisher, Janet L

    2010-03-01

    The GABA(A) receptors are ligand-gated chloride channels which are the targets for many clinically used sedatives, including the barbiturates. The barbiturate pentobarbital acts through multiple sites on the GABA(A) receptor. At low concentrations (muM), it acts as a positive allosteric modulator while at higher concentrations it can directly activate the receptor. This agonist action is influenced by the subunit composition of the receptor, and pentobarbital is a more effective agonist than GABA only at receptors containing an alpha6 subunit. The conformational change that translates GABA binding into channel opening is known to involve a lysine residue located in an extracellular domain between the 2nd and 3rd transmembrane domains. Mutations of this residue disrupt activation of the channel by GABA and have been linked to inherited epilepsy. Pentobarbital binds to the receptor at a different agonist site than GABA, but could use a common signal transduction mechanism to gate the channel. To address this question, we compared the effect of a mutating the homologous lysine residue in the alpha1 or alpha6 subunits (K278 or K277, respectively) to methionine on direct activation of recombinant GABA(A) receptors by GABA or pentobarbital. We found that this mutation reduced GABA sensitivity for both alpha1 and alpha6 subunits, but affected pentobarbital sensitivity only for the alpha1 subunit. This suggests that pentobarbital acts through a distinct signal transduction pathway at the alpha6 subunit, which may account for its greater efficacy compared to GABA at receptors containing this subunit. PMID:20109529

  6. The effects of chlorpromazine and pentobarbital on behavior maintained by electric shock or point loss avoidance in humans.

    PubMed

    Fischman, M W; Schuster, C R

    1979-01-01

    Human volunteer subjects were trained to press a lever to avoid or escape electric shock or loss of points which could be redeemed for money at the termination of the study. The effects of pentobarbital and chlorpromazine on avoidance and escape behavior were compared. Both aversive stimuli maintained behavior which was differentially sensitive to these two drugs. Chlorpromazine caused a decrease in avoidance responding at doses which had little effect on escape responding. Pentobarbital, in contrast, suppressed avoidance responding at doses which also had a suppressant effect on escape responding. PMID:120538

  7. Effects of anesthetics pentobarbital sodium and chloral hydrate on urine proteome

    PubMed Central

    Zhao, Mindi; Li, Xundou; Li, Menglin

    2015-01-01

    Urine can be a better source than blood for biomarker discovery since it accumulates many changes. The urine proteome is susceptible to many factors, including anesthesia. Pentobarbital sodium and chloral hydrate are commonly used anesthetics in animal experiments. This study demonstrated the effects of these two anesthetics on the rat urine proteome using liquid chromatography–tandem mass spectrometry (LC-MS/MS). With anesthesia, the urinary protein-to-creatinine ratio of all rats increased twofold. The relative abundance of 22 and 23 urinary proteins were changed with pentobarbital sodium or chloral hydrate anesthesia, respectively, as determined by label-free quantification. Among these changed proteins, fifteen had been considered as candidate biomarkers such as uromodulin, and sixteen had been considered stable in healthy human urine, which are more likely to be considered as potential biomarkers when changed, such as transferrin. The pattern of changed urinary proteins provides clues to the discovery of urinary proteins regulatory mechanisms. When determining a candidate biomarker, anesthetic-related effects can be excluded from future biomarker discovery studies. Since anesthetics take effects via nervous system, this study is the first to provide clues that the protein handling function of the kidney may possibly be regulated by the nervous system. PMID:25789206

  8. Hypnotic Hypersensitivity to Volatile Anesthetics and Dexmedetomidine in Dopamine β-Hydroxylase Knockout Mice

    PubMed Central

    Hu, Frances Y.; Hanna, George M.; Han, Wei; Mardini, Feras; Thomas, Steven A.; Wyner, Abraham J.; Kelz, Max B.

    2012-01-01

    BACKGROUND Multiple lines of evidence suggest that the adrenergic system can modulate sensitivity to anesthetic-induced immobility and anesthetic-induced hypnosis as well. However, several considerations prevent the conclusion that the endogenous adrenergic ligands norepinephrine and epinephrine alter anesthetic sensitivity. METHODS Using dopamine β-hydroxylase (Dbh−/−) mice genetically engineered to lack the adrenergic ligands and their siblings with normal adrenergic levels, we test the contribution of the adrenergic ligands upon volatile anesthetic induction and emergence. Moreover, we investigate the effects of intravenous dexmedetomidine in adrenergic-deficient mice and their siblings using both righting reflex and processed electroencephalographic measures of anesthetic hypnosis. RESULTS We demonstrate that the loss of norepinephrine and epinephrine and not other neuromodulators copackaged in adrenergic neurons is sufficient to cause hypersensitivity to induction of volatile anesthesia. However, the most profound effect of adrenergic deficiency is retarding emergence from anesthesia, which takes two to three times as long in Dbh−/− mice for sevoflurane, isoflurane, and halothane. Having shown that Dbh−/− mice are hypersensitive to volatile anesthetics, we further demonstrate that their hypnotic hypersensitivity persists at multiple doses of dexmedetomidine. Dbh−/− mice exhibit up to 67% shorter latencies to loss of righting reflex and up to 545% longer durations of dexmedetomidine-induced general anesthesia. Central rescue of adrenergic signaling restores control-like dexmedetomidine sensitivity. A novel continuous electroencephalographic analysis illustrates that the longer duration of dexmedetomidine-induced hypnosis is not due to a motor confound, but occurs because of impaired anesthetic emergence. CONCLUSIONS Adrenergic signaling is essential for normal emergence from general anesthesia. Dexmedetomidine-induced general anesthesia does

  9. Damned if you do, damned if you don't? The Lundbeck case of pentobarbital, the guiding principles on business and human rights, and competing human rights responsibilities.

    PubMed

    Buhmann, Karin

    2012-01-01

    In 2011 it emerged that to induce the death penalty, United States authorities had begun giving injections of pentobarbital, a substance provided by Danish pharmaceutical company Lundbeck. Lundbeck's product pentobarbital is licensed for treatment of refractory forms of epilepsy and for usage as an anaesthetic, thus for a very different purpose. The Lundbeck case offers a difficult, but also interesting Corporate Social Responsibility (CSR) dilemma between choices facing a pharmaceutical company to stop the distribution of a medical substance in order to avoid complicity in human rights violations, or to retain distribution of the substance in order not to impede access to the medicine for those patients who need it. The dilemma arose at a time when the United Nations (UN) Secretary General's Special Representative on Business and Human Rights, Professor John Ruggie, was finalizing a set of Guiding Principles to operationalize recommendations on business and human rights that he had presented to the UN Human Rights Council in 2008. The article discusses the dilemma in which Lundbeck was placed in from the perspective of the Guiding Principles on business and human rights and the 2008 Protect, Respect, Remedy UN Framework. The analysis seeks to assess what guidance may be gauged from the Guiding Principles in relation to the dilemma at hand and discusses the adequacy the Guiding Principles for dealing with acute human rights dilemmas of conflicting requirements in which a decision to avoid one type of violation risks causing violation of another human right. The article concludes by drawing up perspectives for further development of guidance on implementation of the UN Framework that could be considered by the newly established Working Group on Business and Human Rights and related UN bodies. PMID:22789041

  10. Role of Beliefs About Hypnotic States as a Moderator Variable: A Reexamination of the Relationship Between Reactance and Hypnotizability.

    PubMed

    Shimizu, Takahiro

    2016-01-01

    The hypothesis that beliefs about hypnosis determine the amount of psychological reactance aroused was tested. Participants were administered a measure of trait reactance to therapist directives (Therapeutic Reactance Scale; TRS), the Beliefs about Hypnotic State Questionnaire (BHSQ-R), and behavioral and subjective scales concerning hypnotic response. Hierarchical multiple regressions revealed significant interactions between BHSQ-R subscales and TRS. The findings suggest that the arousal of psychological reactance to hypnosis is determined by individuals' trait reactance levels acting together with their interpretations of the hypnotic situation. The role of beliefs about hypnotic states as a moderator of the relationship between personality and hypnotizability was discussed. PMID:26894421

  11. Antidepressants, anxiolytics, and hypnotics in pregnancy and lactation

    PubMed Central

    Ram, Daya; Gandotra, S.

    2015-01-01

    Aims: Untreated perinatal depression and anxiety disorders are known to have significant negative impact on both maternal and fetal health. Dilemmas still remain regarding the use and safety of psychotropics in pregnant and lactating women suffering from perinatal depression and anxiety disorders. The aim of the current paper was to review the existing evidence base on the exposure and consequences of antidepressants, anxiolytics, and hypnotics in women during pregnancy and lactation and to make recommendations for clinical decision making in management of these cases. Materials and Methods: We undertook a bibliographic search of Medline/PubMed (1972 through 2014), Science Direct (1972 through 2014), Archives of Indian Journal of Psychiatry databases was done. References of retrieved articles, reference books, and dedicated websites were also checked. Results and Conclusions: The existing evidence base is extensive in studying multiple outcomes of the antidepressant or anxiolytic exposure in neonates, and some of the findings appear conflicting. Selective serotonin reuptake inhibitors are the most researched antidepressants in pregnancy and lactation. The available literature is criticized mostly on the lack of rigorous well designed controlled studies as well as lacunae in the methodologies, interpretation of statistical information, knowledge transfer, and translation of information. Research in this area in the Indian context is strikingly scarce. Appropriate risk-benefit analysis of untreated mental illness versus medication exposure, tailor-made to each patient's past response and preference within in the context of the available evidence should guide clinical decision making. PMID:26330654

  12. Possibilities and problems with identification and determination of "new" hypnotics.

    PubMed

    Ondra, Peter; Zedníková, Katerina; Matlach, Radek

    2005-12-01

    Authors discuss problems with identification and determination of flunitrazepam and zolpidem in biological material (BM). Over the recent years, these two structurally different substances have become the most frequently used as well as abused hypnotic drugs. This study presents applicability of immunochemical methods in the screening of flunitrazepam, one of the most commonly prescribed drugs among the benzodiazepines. Herein described techniques, a liquid-liquid (L-L) extraction, solid phase extraction (SPE) and the so-called "freeze out" method are used for isolation of the above mentioned compounds from BM. Besides the thin layer chromatography (TLC) and gas chromatography - mass spectrometry (GC-MS) applied in qualitative analysis, the study also describes a gas chromatography with electron capture detector (GC-ECD) and gas chromatography with nitrogen phosphorus detector (GC-NPD) optimized for the determination of flunitrazepam and zolpidem in blood (serum). Successful analyses of these two substances are of major importance, especially in interpreting the results of forensic toxicological examinations. PMID:16601812

  13. The ameliorative effects of a hypnotic bromvalerylurea in sepsis.

    PubMed

    Kikuchi, Satoshi; Nishihara, Tasuku; Kawasaki, Shun; Abe, Naoki; Kuwabara, Jun; Choudhury, Mohammed E; Takahashi, Hisaaki; Yano, Hajime; Nagaro, Takumi; Watanabe, Yuji; Aibiki, Mayuki; Tanaka, Junya

    2015-04-01

    Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF. PMID:25732089

  14. Hypnotic modulation of resting state fMRI default mode and extrinsic network connectivity.

    PubMed

    Demertzi, A; Soddu, A; Faymonville, M-E; Bahri, M A; Gosseries, O; Vanhaudenhuyse, A; Phillips, C; Maquet, P; Noirhomme, Q; Luxen, A; Laureys, S

    2011-01-01

    Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to self-related processes) and an anticorrelated "extrinsic" system (encompassing lateral frontoparietal areas and modulated via external sensory stimulation). In order to better determine the functional contribution of these networks to conscious awareness, we here sought to transiently modulate their relationship by means of hypnosis. We used independent component analysis (ICA) on resting state fMRI acquisitions during normal wakefulness, under hypnotic state, and during a control condition of autobiographical mental imagery. As compared to mental imagery, hypnosis-induced modulation of resting state fMRI networks resulted in a reduced "extrinsic" lateral frontoparietal cortical connectivity, possibly reflecting a decreased sensory awareness. The default mode network showed an increased connectivity in bilateral angular and middle frontal gyri, whereas its posterior midline and parahippocampal structures decreased their connectivity during hypnosis, supposedly related to an altered "self" awareness and posthypnotic amnesia. In our view, fMRI resting state studies of physiological (e.g., sleep or hypnosis), pharmacological (e.g., sedation or anesthesia), and pathological modulation (e.g., coma or related states) of "intrinsic" default mode and anticorrelated "extrinsic" sensory networks, and their interaction with other cerebral networks, will further improve our understanding of the neural correlates of subjective awareness. PMID:21854971

  15. Oxytocin impedes the effect of the word blindness post-hypnotic suggestion on Stroop task performance.

    PubMed

    Parris, Benjamin A; Dienes, Zoltan; Bate, Sarah; Gothard, Stace

    2014-07-01

    The ability to enhance sensitivity to relevant (post)hypnotic suggestions has implications for creating clinically informed analogues of psychological and neuropsychological conditions and for the use of hypnotic interventions in psychological and medical conditions. The aim of this study was to test the effect of oxytocin inhalation on a post-hypnotic suggestion that previously has been shown to improve the selectivity of attention in the Stroop task. In a double-blind placebo-controlled between-subjects study, medium hypnotizable individuals performed the Stroop task under normal conditions and when they had been given a post-hypnotic suggestion that they would perceive words as meaningless symbols. In line with previous research, Stroop interference was substantially reduced by the suggestion in the placebo condition. However, contrary to expectations, oxytocin impeded the effect of the word blindness suggestion on performance. The results are explained in terms of the requirement for the re-implementation of the word blindness suggestion on a trial-by-trial basis and the need to sustain activation of the suggestion between trials. The findings contrast with a recent study showing a beneficial effect of oxytocin on sensitivity to (post)hypnotic suggestions but are consistent with findings showing a detrimental effect of oxytocin on memory processes. PMID:23620599

  16. Meperidine-acepromazine-pentobarbital anesthesia in cats: reversal by 4-aminopyridine and yohimbine.

    PubMed

    Hatch, R C; Zahner, J M; Booth, N H

    1984-12-01

    Groups of atropinized cats (6/group) were given IM meperidine (5.5 mg/kg of body weight) plus acepromazine (0.25 mg/kg). Forty minutes later, the cats were anesthetized to disappearance of pedal reflexes with 1% pentobarbital IV. Volume of anesthetic was recorded. Five minutes later, the cats were given IV saline solution (2 ml; control group), the antagonists 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), or a combination of 0.5 mg of 4-AP/kg plus 0.4 mg of yohimbine/kg. Mean arousal time (MAT), walk time (MWT), respiratory rate, and heart rate were measured. Emergence phenomena also were recorded. Meperidine plus acepromazine caused mydriasis and mild sedation without ataxia or marked protrusion of the 3rd eyelid. The cats did not resist restraint for venipuncture. The pooled mean dosage level of pentobarbital required for anesthesia was 12.3 mg/kg. Control group MAT and MWT were 66.2 minutes and 126 minutes, respectively. Marked residual sedation lasted several hours. In cats given 4-AP plus yohimbine, MAT and MWT were decreased to 4.4 minutes and 36.5 minutes, respectively. These values were not significantly shorter than those same values in cats given 4-AP or yohimbine alone (P greater than 0.05), but the combination of 4-AP plus yohimbine produced a qualitatively better reversal of anesthesia than did 4-AP or yohimbine alone. Emergence was smooth in all 4 groups; mild-to-moderate residual sedation lasted 2 to 4 hours in the principals. Relapses, drug side effects, and behavioral aberrations were not observed. Mean respiratory rates and heart rates decreased during anesthesia but these values were not excessively depressed or stimulated at any time. Cardiac irregularities were not detected by palpation or auscultation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6524759

  17. Intravenous Hypnotic Regimens in Patients With Liver Disease; A Review Article

    PubMed Central

    Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Jafari Rouhi, Asghar; Alavian, Seyed Moayed

    2015-01-01

    Context: The liver as an important organ in the body has many essential functions in physiological processes. One of the major activities of liver is drug metabolism. Hepatic dysfunction affecting hepatic physiological activities, especially drug metabolism can cause many problems during anesthesia and administration of different drugs to patients. Evidence Acquisition: Studies on hepatic disorders and hypnotic anesthetics prescribed in hepatic disorders were included in this review. For this purpose, reliable databases were used. Results: Anesthesia should be performed with caution in patients with hepatic dysfunction and drugs with long half-life should be avoided in these patients. Conclusions: A review of the literature on the use of hypnotic drugs in patients with liver dysfunction showed that some hypnotic drugs used during anesthesia could be safely used in patients with impaired liver function. In these patients, certain drugs should be used with caution. PMID:25793176

  18. A Comparison of Hypnotic Induction, Task Motivation, and a "Cold Start" Control Group on Hypnotizability.

    PubMed

    Krystek, Stephen; Kumar, V K

    2016-10-01

    Groups of participants (N = 164) were randomly assigned to three conditions: Group 1 received a trance induction, Group 2 received task-motivational instructions, and Group 3-"cold start" control-was simply told, "We will begin the hypnosis procedure now." All participants received the Creative Imagination Scale suggestions and then completed the Creative Imagination Scale and Inventory Scale of Hypnotic Depth. The three conditions did not differ significantly either on the Creative Imagination Scale or in reported hypnotic depth. These results are consistent with prior studies which show that trance induction and task-motivational yield similar results, but they are inconsistent inasmuch as the trance induction and task-motivational groups did not differ from the control group. These results, however, are predictable from socio-cognitive perspectives that the context of hypnosis itself can elicit hypnotic behaviors. PMID:27586049

  19. Norms for the Korean version of the Harvard Group Scale of Hypnotic Susceptibility, Form A.

    PubMed

    Pyun, Young Don; Kim, Yun Joo

    2009-01-01

    The Korean Version of the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:K) was adapted and studied in order to determine Korean norms. In total, 271 subjects (175 males and 96 females) participated in the study. Comparisons are made between the Korean samples and previously published international samples. The normative data from the Korean sample on the HGSHS:K are generally congruent, including means and standard deviations, with data from international reference samples. However, the pass rate on the hallucination item on the Harvard Group Scale of Hypnotic Susceptibility, Form A, was significantly different from that of the American sample. Females showed higher overall scores than males. PMID:19031236

  20. An Update on the Use of Sedative-Hypnotic Medications in Psychiatric Disorders.

    PubMed

    Creado, Shane; Plante, David T

    2016-09-01

    Sleep disturbance is a common clinical problem experienced by patients with a wide range of psychiatric disorders. Accumulating evidence has demonstrated that insomnia is a comorbid process that affects the course and treatment of a number of forms of mental illness. The efficacy and safety of sedative-hypnotic medications have largely been established in patients who do not have comorbid psychiatric disorders, underscoring the need for further research in this sphere. This review summarizes pertinent findings in the recent literature that have examined the role of hypnotic medication in the treatment of psychiatric illness, and highlights potential areas that may prove fruitful avenues of future research. PMID:27417512

  1. Gilles de la Tourette's criminal women: the many faces of fin de siècle hypnotism.

    PubMed

    Bogousslavsky, Julien; Walusinski, Olivier

    2010-09-01

    Gilles de la Tourette is now known for the disease which now bears his name, but his activities in the management of hysterics and in hypnotism, which gained him most of his lifetime reputation, have been largely forgotten. As one of the closest followers of Jean-Martin Charcot, he always remained faithful to his mentor's views, and was one of the most vehement defenders of La Salpêtrière school during the quarrel with Hippolyte Bernheim and the Nancy school on the question of the specificity of hypnotic susceptibility in hysteria. This controversy became critical during medico-legal assessment of crimes supposedly committed under hypnotic suggestion. Gilles de la Tourette's involvement in criminal hypnotism was striking, as shown by his own experiments, the most famous of which being his suggested poisoning of a colleague by Blanche Wittman, the celebrated Charcot's hysteric patient in the 1887 Brouillet's painting. Gilles de la Tourette also acted as expert in murder trials, and his Epilogue in the Gouffé's trunk case, where he affirmed that no murder in real life could be due to hypnotism, and considered that Gabrielle Bompard, the murderer's accomplice, was not under hypnotic suggestion, had a considerable impact. Finally, he was confronted to the issue of murder under hypnotism in his private life, since in 1893, a former patient, Rose Kamper, came and shot him in the head at his home, claiming that hypnotism sessions had changed her own person, and that she had been hypnotized "at distance". These acts from three very different "hysterical" women highlight the Salpêtrière's theories on hypnotism and their inner contradictions in the fin de siècle ambiance, a few years before Joseph Babinski renewed the concepts on hysteria. PMID:20413214

  2. Activity of the hypnotics, flunitrazepam and triazolam, in man

    PubMed Central

    Nicholson, A. N.; Stone, Barbara M.

    1980-01-01

    1 Effects of flunitrazepam and triazolam (0.25 and 0.5 mg) on sleep and on performance were studied in six healthy adult males. Sleep was assessed by electroencephalography and analogue scales, and performance by a visuo-motor coordination task. 2 Over the same dose range triazolam had a more pronounced effect than flunitrazepam. Total sleep time was increased by 0.25 and 0.5 mg triazolam, and by 0.5 mg flunitrazepam. Both drugs decreased awake activity and drowsy sleep, though the effect of flunitrazepam was limited to the 0.5 mg dose and restricted to the first 6 h after sleep onset. There were no changes in slow wave sleep. 3 Latency to the first period of rapid eye movement (REM) sleep was increased with 0.5 mg triazolam, and when doses were combined (0.25-0.5 mg) the latencies with both drugs were increased. Both doses of triazolam reduced the duration and percentage of REM sleep during the early part of the night, though the whole night duration of REM sleep was not changed. 4 After the morning ingestion of 0.25 mg flunitrazepam performance was impaired for 2.0 h, but there were no residual effects when 0.25 or 0.5 mg were taken at night. With the morning ingestion of 0.25 mg triazolam performance was impaired from 0.5 to at least 5.0 h after ingestion. There were no residual effects with 0.25 mg overnight, but with 0.5 mg triazolam there was an effect on performance 10 h after ingestion with recovery within 1.5 h (11.5 h of ingestion). 5 Triazolam (0.25 mg) and 0.5 mg flunitrazepam provide useful hypnotic activity when impaired performance the next day is to be avoided. The activity of 0.5 mg triazolam is accompanied by only limited residual sequelae compared with some other benzodiazepines of comparable efficacy, and so may prove to be useful when a more powerful effect is required. PMID:6101959

  3. Hypnotic Depth and the Incidence of Emergence Agitation and Negative Postoperative Behavioral Changes

    PubMed Central

    Faulk, Debra J.; Twite, Mark D.; Zuk, Jeannie; Pan, Zhaoxing; Wallen, Brett; Friesen, Robert H.

    2011-01-01

    Background Emergence agitation (EA) and negative postoperative behavioral changes (NPOBC) are common in children, though the etiology remains unclear. We investigated whether longer times under deep hypnosis as measured by Bispectral Index™ (BIS) monitoring would positively correlate with a greater incidence of EA in the post anesthesia care unit (PACU) and a greater occurrence of NPOBC in children after discharge. Methods We enrolled 400 children, ages 1–12 years old, scheduled for dental procedures under general anesthesia. All children were induced with high concentration sevoflurane and BIS monitoring was continuous from induction through recovery in the PACU. A BIS reading <45 was considered deep hypnosis. The presence of EA was assessed in the PACU using the Pediatric Anesthesia Emergence Delirium Scale (PAED). NPOBC were assessed using the Post-Hospital Behavior Questionnaire (PHBQ), completed by parents 3–5 days post-operatively. Data were analyzed using logistic regression, with a p<0.05 considered statistically significant. Results The incidence of EA was 27% (99/369) and the incidence of NPOBC was 8.8% (28/318). No significant differences in the incidence of EA or NPOBC were seen with respect to length of time under deep hypnosis as measured by a BIS value of less than 45. Conclusion Our data revealed no significant correlation between the length of time under deep hypnosis (BIS<45) and the incidence of EA or NPOBC. Within this population, these behavioral disturbances do not appear to be related to the length of time under a deep hypnotic state as measured by the BIS. PMID:19968807

  4. Role of histaminergic neurons in hypnotic modulation of brain processing of visceral perception.

    PubMed

    Watanabe, S; Hattori, T; Kanazawa, M; Kano, M; Fukudo, S

    2007-10-01

    Modulating visceral sensation of the body is important to the understanding of emotion formation. Molecules that act during hypnosis and modify visceral pain perception are not known. We tested our hypothesis that hypnotic suggestion changes electrophysiological processing of visceroafferent signals in the human brain and that these conditions are in part dependent on histaminergic neurons. Twelve healthy male subjects were studied on two separate days: a day of treatment with histamine H1 receptor antagonist (d-chlorpheniramine 100 microg kg(-1), intravenously) and another day of that with placebo (saline, the same amount) in a randomized order. We recorded cortical evoked potentials to 100 rectal electrical stimuli after neutral, hyperalgesic or analgesic hypnotic suggestions as given to modulate the visceral perception. Analgesic suggestion reduced the amplitude of the deepest positive peak of viscerosensory evoked potential. Administration of histamine H1 antagonist diminished the attenuation of viscerosensory evoked potential by analgesic suggestion. Our results suggest that central pain modulatory system in the brain is activated by hypnotic suggestion and that brain histamine is a mediator in the hypnotic modulation of visceral sensory pathway as well as in the control of consciousness level. These findings lead us to possible new treatment for control of visceral perception. PMID:17883434

  5. Achievement Motivation, Socialization, and Hypnotic Susceptibility Among Youths from Four Israeli Subcultures

    ERIC Educational Resources Information Center

    Rotenberg, Mordechai; And Others

    1976-01-01

    The impact of child rearing practices on achievement motivation, hypnotic susceptibility, and brain wave patterns of children from Israeli subcultures are examined. Of the four subgroups studied, although they differed in school performance, their need achievement scores were similiar. (Author/DEP)

  6. The Role of Expectancy in Eliciting Hypnotic Responses as a Function of Type of Induction.

    ERIC Educational Resources Information Center

    Kirsch, Irving; And Others

    1984-01-01

    Examined the relationship between expectancy and suggestibility in hypnosis as a function of type of induction (N=100). Results showed subjects were able to predict their responses to a cognitive skill induction with great accuracy but were not very accurate in predicting responses to a hypnotic trance induction. (JAC)

  7. Experiential Response to Auditory and Visual Hallucination Suggestions in Hypnotic Subjects

    ERIC Educational Resources Information Center

    Spanos, Nicholas P.; And Others

    1976-01-01

    The effects of several attitudinal, cognitive skill, and personality variables in response to auditory and visual hallucination suggestions to hypnotic subjects are assessed. Cooperative attitudes toward hypnosis and involvement in everyday imaginative activities (absorption) correlated with response to auditory and visual hallucination…

  8. Psychological Treatment of Hypnotic-Dependent Insomnia in a Primarily Older Adult Sample

    PubMed Central

    Lichstein, Kenneth L.; Nau, Sidney D.; Wilson, Nancy M.; Aguillard, R. Neal; Lester, Kristin W.; Bush, Andrew J.; McCrae, Christina S.

    2013-01-01

    Objective This study tested cognitive behavior therapy (CBT) in hypnotic-dependent, late middle-age and older adults with insomnia. Method Seventy volunteers age 50 and older were randomized to CBT plus drug withdrawal, placebo biofeedback (PL) plus drug withdrawal, or drug withdrawal (MED) only. The CBT and PL groups received eight, 45 minute weekly treatment sessions. The drug withdrawal protocol comprised slow tapering monitored with about six biweekly, 30 minute sessions. Assessment including polysomnography (PSG), sleep diaries, hypnotic consumption, daytime functioning questionnaires, and drug screens collected at baseline, posttreatment, and 1-year follow-up. Results Only the CBT group showed significant sleep diary improvement, sleep onset latency significantly decreased at posttreatment. For all sleep diary measures for all groups, including MED, sleep trended to improvement from baseline to follow-up. Most PSG sleep variables did not significantly change. There were no significant between group differences in medication reduction. Compared to baseline, the three groups decreased hypnotic use at posttreatment, down 84%, and follow-up, down 66%. There was no evidence of withdrawal side-effects. Daytime functioning, including anxiety and depression, improved by posttreatment. Rigorous methodological features, including documentation of strong treatment implementation and the presence of a credible placebo, elevated the confidence due these findings. Conclusions Gradual drug withdrawal was associated with substantial hypnotic reduction at posttreatment and follow-up, and withdrawal side-effects were absent. When supplemented with CBT, participants accrued incremental self-reported, but not PSG, sleep benefits. PMID:24121096

  9. Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

    SciTech Connect

    Lai, H.; Prather, P.L. )

    1990-02-26

    Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.

  10. The Use of Hypnotics and Mortality - A Population-Based Retrospective Cohort Study

    PubMed Central

    Lan, Tzuo-Yun; Zeng, Ya-Fang; Tang, Gau-Jun; Kao, Hui-Chuan; Chiu, Hsien-Jane; Lan, Tsuo-Hung; Ho, Hsiao-Feng

    2015-01-01

    Background Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality. Methods We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations. Results Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78–1.85) and mixed users (HR = 1.44; 95% CI = 1.42–1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71–0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk. Conclusions The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality. PMID:26709926

  11. Network actions of pentobarbital in the rat mesopontine tegmentum on sensory inflow through the spinothalamic tract.

    PubMed

    Namjoshi, Dhananjay R; McErlane, Shelly A; Taepavarapruk, Niwat; Soja, Peter J

    2009-08-01

    The recent discovery of a barbiturate-sensitive "general anesthesia switch" mechanism localized in the rat brain stem mesopontine tegmental anesthesia area (MPTA) has challenged the current view of the nonspecific actions of general anesthetic agents in the CNS. In this study we provide electrophysiological evidence that the antinociception, which accompanies the behavioral state resembling general anesthesia following pentobarbital (PB) microinjections into the MPTA of awake rats, could be accompanied by the attenuation of sensory transmission through the spinothalamic tract (STT). Following bilateral microinjections of PB into the MPTA spontaneous firing rate (SFR), antidromic firing index (FI), and sciatic (Sc) as well as sural (Su) nerve-evoked responses (ER) of identified lumbar STT neurons in the isoflurane-anesthetized rat were quantified using extracellular recording techniques. Microinjections of PB into the MPTA significantly suppressed the SFR (47%), magnitudes of Sc- (26%) and Su-ER (36%), and FI (41%) of STT neurons. Microinjections of PB-free vehicle control did not alter any of the above-cited electrophysiological parameters. The results from this study suggest that antinociception, which occurs during the anesthesia-like state following PB microinjections into the MPTA, may be due, in part, to (in)direct inhibition of STT neurons via switching mechanism(s) located in the MPTA. This study provides a provenance for investigating electrophysiologically the actions on STT neurons of other current agents used clinically to maintain the state of general anesthesia. PMID:19458144

  12. Pentobarbital Toxicity after Self-Administration of Euthasol Veterinary Euthanasia Medication.

    PubMed

    Crellin, Steven Jason; Katz, Kenneth D

    2016-01-01

    Suicide attempt via sodium pentobarbital is uncommon. A 48-year-old woman with a history of depression and prior suicide attempt was found unresponsive by her veterinarian spouse near a syringe containing pink solution. Upon EMS' arrival, the patient was experiencing apnea, hypoxemia, and miotic pupils; her blood glucose level measured 73 mg/dL. She was bradycardic and administered atropine with transient improvement in heart rate and transported to an emergency department; 2 mg of intravenous naloxone was administered without effect. She was endotracheally intubated via rapid sequence intubation. Rapid urine drug screening detected both benzodiazepines and barbiturates. The patient was transferred to an intensive care unit where she demonstrated a nearly absent radial pulse. Emergent fasciotomy to the left forearm and carpal tunnel was performed for acute compartment syndrome; "Euthasol" had been self-administered into the antecubital fossa. Expanded toxicological analysis via liquid chromatography/mass spectroscopy detected caffeine, atropine, 7-aminoclonazepam, phenytoin, citalopram, and naproxen. The patient's coma resolved over 48 hours and she was successfully extubated without complication. Emergency physicians must closely monitor patients exposed to veterinary euthanasia agents who develop central nervous system and respiratory depression, hypothermia, bradycardia, hypotension, or skin injury. Consultation with a regional poison center and medical toxicologist is recommended. PMID:26881149

  13. Pentobarbital Toxicity after Self-Administration of Euthasol Veterinary Euthanasia Medication

    PubMed Central

    Crellin, Steven Jason; Katz, Kenneth D.

    2016-01-01

    Suicide attempt via sodium pentobarbital is uncommon. A 48-year-old woman with a history of depression and prior suicide attempt was found unresponsive by her veterinarian spouse near a syringe containing pink solution. Upon EMS' arrival, the patient was experiencing apnea, hypoxemia, and miotic pupils; her blood glucose level measured 73 mg/dL. She was bradycardic and administered atropine with transient improvement in heart rate and transported to an emergency department; 2 mg of intravenous naloxone was administered without effect. She was endotracheally intubated via rapid sequence intubation. Rapid urine drug screening detected both benzodiazepines and barbiturates. The patient was transferred to an intensive care unit where she demonstrated a nearly absent radial pulse. Emergent fasciotomy to the left forearm and carpal tunnel was performed for acute compartment syndrome; “Euthasol” had been self-administered into the antecubital fossa. Expanded toxicological analysis via liquid chromatography/mass spectroscopy detected caffeine, atropine, 7-aminoclonazepam, phenytoin, citalopram, and naproxen. The patient's coma resolved over 48 hours and she was successfully extubated without complication. Emergency physicians must closely monitor patients exposed to veterinary euthanasia agents who develop central nervous system and respiratory depression, hypothermia, bradycardia, hypotension, or skin injury. Consultation with a regional poison center and medical toxicologist is recommended. PMID:26881149

  14. Treatment outcome expectancies and hypnotic susceptibility as moderators of pain reduction in patients with chronic tension-type headache.

    PubMed

    Spinhoven, P; ter Kuile, M M

    2000-07-01

    The aim of this study was to determine whether hypnotic susceptibility (a) predicts pain reduction posttreatment and at follow-up independent of generic expectations of treatment outcome and mode of treatment and (b) predicts persistence of pain reduction during the follow-up period. In 169 patients with chronic tension-type headaches randomly allocated to either self-hypnosis or autogenic training, pain reduction posttreatment and at follow-up was significantly associated with hypnotic susceptibility independent of generic expectations of treatment outcome and treatment condition. Moreover, it was found that early responders obtained significantly higher hypnotic susceptibility scores than nonresponders, although there were no significant differences in hypnotic susceptibility between late responders in comparison to early and nonresponders. However, almost one fourth of those who were nonresponders posttreatment did respond at follow-up. PMID:10902294

  15. A comparison of the clinical effectiveness of various acupuncture points in reducing anxiety to facilitate hypnotic induction.

    PubMed

    Lu, Dominic P; Lu, Gabriel P

    2013-01-01

    This study determined if any acupuncture point (acupoint) known for its calming effects also aided hypnotic induction. Hypnosis was offered to 108 patients requiring minor surgical or dental procedures. All had a history of panic attacks and surgical or dental phobias that complicated or prevented treatment. Unpleasant intruding thoughts of imminent invasive treatments handicapped their ability to accept hypnotic induction; however, acupuncture therapy was proposed to the consenting patient to facilitate hypnotic induction and augment its effects. Each patient received one selected acupoint for acupuncture therapy. Of the 6 acupoints used (LI 4, H 7, SP 6, P 6, GV 24, and Ext-hn-21), GV 24 was best at enhancing hypnotic induction whereas LI 4 produced the best muscular relaxation and P 6 for reducing tension. PMID:23679111

  16. Study of Sedative-Hypnotic Effects of Aloe vera L. Aqueous Extract through Behavioral Evaluations and EEG Recording in Rats

    PubMed Central

    Abdollahnejad, Fatemeh; Mosaddegh, Mahmoud; Nasoohi, Sanaz; Mirnajafi-Zadeh, Javad; Kamalinejad, Mohammad; Faizi, Mehrdad

    2016-01-01

    In this study, we investigated the sedative and hypnotic effects of the aqueous extract of Aloe vera on rats. In order to evaluate the overall hypnotic effects of the Aloe vera extract, open field and loss of righting reflex tests were primarily used. The sedative and hypnotic effects of the extract were then confirmed by detection of remarkable raise in the total sleeping time through analysis of electroencephalographic (EEG) recordings of animals. Analysis of the EEG recordings showed that there is concomitant change in Rapid Eye Movement (REM) and None Rapid Eye Movement (NREM) sleep in parallel with the prolonged total sleeping time. Results of the current research show that the extract has sedative-hypnotic effects on both functional and electrical activities of the brain. PMID:27610170

  17. Study of Sedative-Hypnotic Effects of Aloe vera L. Aqueous Extract through Behavioral Evaluations and EEG Recording in Rats.

    PubMed

    Abdollahnejad, Fatemeh; Mosaddegh, Mahmoud; Nasoohi, Sanaz; Mirnajafi-Zadeh, Javad; Kamalinejad, Mohammad; Faizi, Mehrdad

    2016-01-01

    In this study, we investigated the sedative and hypnotic effects of the aqueous extract of Aloe vera on rats. In order to evaluate the overall hypnotic effects of the Aloe vera extract, open field and loss of righting reflex tests were primarily used. The sedative and hypnotic effects of the extract were then confirmed by detection of remarkable raise in the total sleeping time through analysis of electroencephalographic (EEG) recordings of animals. Analysis of the EEG recordings showed that there is concomitant change in Rapid Eye Movement (REM) and None Rapid Eye Movement (NREM) sleep in parallel with the prolonged total sleeping time. Results of the current research show that the extract has sedative-hypnotic effects on both functional and electrical activities of the brain. PMID:27610170

  18. Influence of self-induced hypnosis on thermal responses during immersion in 25 degrees C water.

    PubMed

    Mittleman, K D; Doubt, T J; Gravitz, M A

    1992-08-01

    The efficacy of self-induced post-hypnotic suggestion to improve thermogenic responses to head-out immersion in 25 degrees C water was evaluated in 12 males. An on-line computerized system permitted the change in body heat storage to be used as the independent variable and immersion time as the dependent variable. Test-retest reliability was good, exhibiting a coefficient of variation of less than 5% for exposure time. Immersion profiles consisted of the following: rest until 200 kJ of heat were lost, leg exercise at VO2 approximately 1.5 L.min-1 to regain 200 kJ, rest until 100 kJ were lost, and repeat the exercise to regain 100 kJ. A control immersion was done prior to two 1-h hypnotic training sessions. A second immersion (hypnotic) occurred within 24 h after training. There were no differences in rates of heat production, heat loss, mean skin temperature, or rectal temperature between control and hypnotic immersions. Individual hypnotic susceptibility scores did not correlate with changes in thermal status. Ratings of perceived exertion during exercise were similar for both immersions, but perceived sensation of cold was lower during the second rest period of the hypnotic immersion. Three subjects used images of warm environments during their hypnotic immersion and lost heat at a faster rate than during control immersions. These results indicate that brief hypnotic training did not enhance the thermogenic response to cool water immersion. PMID:1510642

  19. Self-administration of cocaine-pentobarbital mixtures by rhesus monkeys.

    PubMed

    Woolverton, W L; Wang, Zhixia

    2009-03-01

    A number of experiments have evaluated self-administration of the combination of a stimulant and an opioid. Less is known about the combination of a stimulant and a CNS depressant. The present experiment was designed to examine self-administration of the mixture of cocaine and pentobarbital (PB). Rhesus monkeys (n=4) prepared with i.v. catheters were allowed to self-administer cocaine or saline under a progressive-ratio schedule. When responding was stable, doses of cocaine and PB, alone or in combination, were made available in test sessions. Cocaine functioned as a positive reinforcer in a dose-related manner in all monkeys. PB functioned as a relatively weaker reinforcer in one of four monkeys. Self-administration of intermediate doses of cocaine (0.025-0.1mg/kg per injection) was decreased when mixed with PB (0.05-0.2mg/kg per injection); full maximum responding was re-established when cocaine dose was increased. The magnitude of the shift to the right in the cocaine dose-response function was directly related to PB dose. When PB was given as an i.v. pretreatment there was no effect on cocaine self-administration up to a sedative dose of PB (5.6 mg/kg), suggesting that responding was not non-specifically suppressed by PB. Thus, simultaneous self-administration of PB diminished the potency but not the strength of cocaine as a reinforcer, potentially encouraging self-administration of larger doses of cocaine. PMID:19054630

  20. Chinese medicines with sedative-hypnotic effects and their active components.

    PubMed

    Shi, Man-Man; Piao, Jin-Hua; Xu, Xi-Lin; Zhu, Liang; Yang, Li; Lin, Fu-Lan; Chen, Jian; Jiang, Jian-Guo

    2016-10-01

    The main pharmacological effects of sedative agents are sedation, hypnosis, antianxiety, and antidepression. Traditional Chinese medicine (TCM) has a long history of clinical experience in treating insomnia. This review focuses mainly on the role of active ingredients from TCM in the treatment of insomnia. Single herbs and their active ingredients from TCM with hypnotic effects are summarized through reviewing the relevant literature published in the past 20 y. The active ingredients are divided into alkaloids, terpenoids, and volatile oils, flavonoids, lignanoids and coumarins, saponins, and others. Current studies on TCM in treating insomnia are described from the aspects of active ingredients, sources, experimental models and methods, results, and mechanisms. In addition, Chinese compound prescriptions developed from a variety of single herbs with sedative-hypnotic effects are introduced. The acting pathways of TCM are covered from the perspectives of regulating central neurotransmitters, influencing sleep-related cytokines, and improving the structure of the central nervous system. PMID:26866454

  1. Anxiety Reduction Among Breast-Cancer Survivors Receiving Hypnotic Relaxation Therapy for Hot Flashes.

    PubMed

    Johnson, Alisa J; Marcus, Joel; Hickman, Kimberly; Barton, Debra; Elkins, Gary

    2016-01-01

    Anxiety is common among breast-cancer survivors. This analysis examined the effect of a hypnotic relaxation therapy, developed to reduce hot flashes, on anxiety levels of female breast-cancer survivors. Anxiety was assessed using a numeric analog scale and the Hospital Anxiety and Depression Scale-Anxiety subscale. Significant reductions in anxiety were found from pre- to postintervention for each weekly session and were predictive of overall reductions in anxiety from baseline to after the last intervention. In this analysis, hypnotizability did not significantly predict for anxiety reductions measured before and after each session or from baseline to exit. These data provide initial support for the use of hypnotic relaxation therapy to reduce anxiety among breast-cancer survivors. PMID:27585723

  2. The neural correlates of movement intentions: A pilot study comparing hypnotic and simulated paralysis.

    PubMed

    Ludwig, Vera U; Seitz, Jochen; Schönfeldt-Lecuona, Carlos; Höse, Annett; Abler, Birgit; Hole, Günter; Goebel, Rainer; Walter, Henrik

    2015-09-01

    The distinct feeling of wanting to act and thereby causing our own actions is crucial to our self-perception as free human agents. Disturbances of the link between intention and action occur in several disorders. Little is known, however, about the neural correlates of wanting or intending to act. To investigate these for simple voluntary movements, we used a paradigm involving hypnotic paralysis and functional magnetic resonance imaging. Eight healthy women were instructed to sequentially perform left and right hand movements during a normal condition, as well as during simulated weakness, simulated paralysis and hypnotic paralysis of the right hand. Right frontopolar cortex was selectively hypoactivated for attempted right hand movement during simulated paralysis while it was active in all other conditions. Since simulated paralysis was the only condition lacking an intention to move, the activation in frontopolar cortex might be related to the intention or volition to move. PMID:26036837

  3. Adverse Respiratory Events Associated With Hypnotics Use in Patients of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Chung, Wei-Sheng; Lai, Ching-Yuan; Lin, Cheng-Li; Kao, Chia-Hung

    2015-01-01

    Abstract Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD). We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD. The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database. Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group. Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex. Patients who had used hypnotics within 1 month meant active users. The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models. Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively. After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11–17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68–14.2) compared with the adjusted ORs of those who never used hypnotics. The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD. PMID:26166105

  4. The Non-Benzodiazepine Hypnotic Zolpidem Impairs Sleep-Dependent Cortical Plasticity

    PubMed Central

    Seibt, Julie; Aton, Sara J.; Jha, Sushil K.; Coleman, Tammi; Dumoulin, Michelle C.; Frank, Marcos G.

    2008-01-01

    Study Objectives: The effects of hypnotics on sleep-dependent brain plasticity are unknown. We have shown that sleep enhances a canonical model of in vivo cortical plasticity, known as ocular dominance plasticity (ODP). We investigated the effects of 3 different classes of hypnotics on ODP. Design: Polysomnographic recordings were performed during the entire experiment (20 h). After a baseline sleep/wake recording (6 h), cats received 6 h of monocular deprivation (MD) followed by an i.p. injection of triazolam (1–10 mg/kg i.p.), zolpidem (10 mg/kg i.p.), ramelteon (0.1–1 mg/kg i.p.), or vehicle (DMSO i.p.). They were then allowed to sleep ad lib for 8 h, after which they were prepared for optical imaging of intrinsic cortical signals and single-unit electrophysiology. Setting: Basic neurophysiology laboratory Patients or Participants: Cats (male and female) in the critical period of visual development (postnatal days 28–41) Interventions: N/A Measurements and Results: Zolpidem reduced cortical plasticity by ∼50% as assessed with optical imaging of intrinsic cortical signals. This was not due to abnormal sleep architecture because triazolam, which perturbed sleep architecture and sleep EEGs more profoundly than zolpidem, had no effect on plasticity. Ramelteon minimally altered sleep and had no effect on ODP. Conclusions: Our findings demonstrate that alterations in sleep architecture do not necessarily lead to impairments in sleep function. Conversely, hypnotics that produce more “physiological” sleep based on polysomnography may impair critical brain processes, depending on their pharmacology. Citation: Seibt J; Aton SJ; Jha SK; Coleman T; Dumoulin MC; Frank MG. The non-benzodiazepine hypnotic zolpidem impairs sleep-dependent cortical plasticity. SLEEP 2008;31(10):1381–1391. PMID:18853935

  5. A concurrent validity study between the Hypnotic Induction Profile (HIP) and the Stanford Hypnotic Clinical Scale for Adults (SHCS:A) in an inpatient sample: a brief report.

    PubMed

    Gritzalis, Nicoletta; Oster, Marc; Frischholz, Edward J

    2009-10-01

    The Hypnotic Induction Profile (HIP) is a brief, standardized assessment of hypnotizability which takes 5-10 minutes to administer. The Stanford Hypnotic Clinical Scale for Adults (SHCS:A) is a different clinical measure of hypnotizability that takes about 20-25 minutes to administer. Although both scales purport to measure the same thing, they were based on different theories of hypnosis and constructed using different psychometric techniques. The present investigation is a concurrent validation study comparing scores on the two instruments in a sample of 24 inpatients. The correlation between the SHCS:A and HIP Induction score was 0.41 (p < .01). However, the Eye Roll Sign (ERS) did not correlate significantly with either the SHCS:A (.04, ns) or the HIP-IND score (-.05, ns). These results indicate that while scores on the HIP and SHCS:A are significantly correlated the inter-correlations are not high enough to consider them as interchangeable measures. Implications of these findings for future research are discussed. PMID:19862895

  6. Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines.

    PubMed

    Stahl, Stephen M

    2008-12-01

    Numerous "antihistamines" as well as various psychotropic medications with antihistamine properties are widely utilized to treat insomnia. Over-the-counter sleep aids usually contain an antihistamine and various antidepressants and antipsychotics with antihistamine properties have sedative-hypnotic actions. Although widely used for the treatment of insomnia, many agents that block the histamine H1 receptor are also widely considered to have therapeutic limitations, including the development of next-day carryover sedation, as well as problems with chronic use, such as the development of tolerance to sedative-hypnotic actions and weight gain. Although these clinical actions are classically attributed to blockade of the H1 receptor, recent findings with H1 selective agents and H1 selective dosing of older agents are challenging these notions and suggest that some of the clinical limitations of current H1-blocking agents at their currently utilized doses could be attributable to other properties of these drugs, especially to their simultaneous actions on muscarinic, cholinergic, and adrenergic receptors. Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics. PMID:19179941

  7. A preconscious neural mechanism of hypnotically altered colors: a double case study.

    PubMed

    Koivisto, Mika; Kirjanen, Svetlana; Revonsuo, Antti; Kallio, Sakari

    2013-01-01

    Hypnotic suggestions may change the perceived color of objects. Given that chromatic stimulus information is processed rapidly and automatically by the visual system, how can hypnotic suggestions affect perceived colors in a seemingly immediate fashion? We studied the mechanisms of such color alterations by measuring electroencephalography in two highly suggestible participants as they perceived briefly presented visual shapes under posthypnotic color alternation suggestions such as "all the squares are blue". One participant consistently reported seeing the suggested colors. Her reports correlated with enhanced evoked upper beta-band activity (22 Hz) 70-120 ms after stimulus in response to the shapes mentioned in the suggestion. This effect was not observed in a control condition where the participants merely tried to simulate the effects of the suggestion on behavior. The second participant neither reported color alterations nor showed the evoked beta activity, although her subjective experience and event-related potentials were changed by the suggestions. The results indicate a preconscious mechanism that first compares early visual input with a memory representation of the suggestion and consequently triggers the color alteration process in response to the objects specified by the suggestion. Conscious color experience is not purely the result of bottom-up processing but it can be modulated, at least in some individuals, by top-down factors such as hypnotic suggestions. PMID:23940663

  8. Are extrasynaptic GABAA receptors important targets for sedative/hypnotic drugs?

    PubMed Central

    Houston, Catriona M; McGee, Thomas P; MacKenzie, Georgina; Troyano-Cuturi, Kevin; Rodriguez, Pablo Mateos; Kutsarova, Elena; Diamanti, Efthymia; Hosie, Alastair M; Franks, Nicholas P; Brickley, Stephen G

    2012-01-01

    High-affinity extrasynaptic GABAA receptors are persistently activated by the low ambient GABA levels that are known to be present in the extracellular space. The resulting tonic conductance generates a form of shunting inhibition that is capable of altering cellular and network behaviour. It has been suggested that this tonic inhibition will be enhanced by neurosteroids, anti-epileptics, and sedative/hypnotic drugs. However, we show that the ability of sedative/hypnotic drugs to enhance tonic inhibition in the mouse cerebellum will critically depend upon ambient GABA levels. For example, we show that the intravenous anaesthetic propofol only enhances tonic inhibition when ambient GABA levels are below 100 nM. More surprisingly, the actions of the sleep promoting drug THIP (4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol) are attenuated at ambient GABA levels of just 20 nM. In contrast, our data suggests that neurosteroid enhancement of tonic inhibition will be greater at high ambient GABA concentrations. We present a model that takes into account realistic estimates of ambient GABA levels and predicted extrasynaptic GABAA numbers when considering the ability of sedative/hypnotic drugs to enhance tonic inhibition. These issues will be important when considering drug strategies designed to target extrasynaptic GABAA receptors in the treatment of sleep disorders and other neurological conditions. PMID:22423109

  9. Sedative and Hypnotic Activities of the Methanolic and Aqueous Extracts of Lavandula officinalis from Morocco.

    PubMed

    Alnamer, Rachad; Alaoui, Katim; Bouidida, El Houcine; Benjouad, Abdelaziz; Cherrah, Yahia

    2012-01-01

    We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this plant was investigated in a battery of behavioural models in mice. Stems and flowers of Lavandula officinalis L. have several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including insomnia. The methanolic extract produced significant sedative effect at the doses of 200, 400, and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP), and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway significantly reduced in both the reestablishment time and number of head dips during the traction and hole-board tests. In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia. PMID:22162677

  10. An Intersubjective View of Empathy and Hypnotic Trance: Response to Wickramasekera II.

    PubMed

    Henning, Janna A

    2016-01-01

    In response to Wickramasekera II's description of his empathic involvement theory of hypnosis in "Mysteries of hypnosis and the self are revealed by the psychology and neuroscience of empathy" (Wickramasekera II, 2015), Henning offers further reflections on what empathy might be and what it allows therapists to do, particularly in conditions of hypnotic trance. She defines her intersubjective view of hypnotic trance as an experience in which client and therapist mutually engage in a shared state of consciousness, and a mutual bidirectional or multidirectional exchange of verbal and nonverbal, as well as conscious and unconscious, material occurs, and which may include shared taking on of roles and expectations in each party, as suggested by the other, particularly when both client and therapist are highly hypnotizable. Research on the concept of "mutual hypnosis," or co-trance, is reviewed, and barriers to scholarly discussions about intersubjectivity in therapy relationships are described. Concepts from other disciplines and traditions, including quantum physics, transpersonal psychology, contemplative Christianity, and shamanistic practices and trance in other cultures are then offered to clarify the processes of intersubjectivity, and perspectives about empathy and hypnotic co-trance are offered from the context of the author's own clinical work as a trauma therapist. Finally, suggestions are provided for future research approaches and methods to further explore and understand these phenomena. PMID:26675153

  11. Nuances and Uncertainties Regarding Hypnotic Inductions: Toward a Theoretically Informed Praxis.

    PubMed

    Terhune, Devin B; Cardeña, Etzel

    2016-10-01

    Although most definitions of hypnosis consider inductions as the initial stage in a hypnosis protocol, knowledge of inductions remains poor and uninformed by recent developments in theory and research. It is frequently argued that inductions play a critical role in hypnotic responding or, by contrast, are largely interchangeable and unimportant. Drawing on the literature on suggestibility, spontaneous phenomenology, neurophysiology, and cognition, this article argues that the value of inductions, as well as the potential value of inductions, is more nuanced and uncertain. Certain components of standard inductions appear to be efficacious in enhancing suggestibility, whereas others do not have any clear benefits. The impact of inductions on suggestibility seems to vary across suggestions and modes of assessment with the sources of this variability being unknown. Considering these effects, and the broader impact of inductions on spontaneous conscious states and cognition, through the lens of heterogeneity in high hypnotic suggestibility and componential models of hypnotic suggestibility may offer novel research avenues in this area. The article concludes by arguing for the practical and theory-driven optimization of inductions. PMID:27586045

  12. "Don't know" responding to answerable and unanswerable questions during misleading and hypnotic interviews.

    PubMed

    Scoboria, Alan; Mazzoni, Giuliana; Kirsch, Irving

    2008-09-01

    "Don't know" (DK) responses to interview questions are conceptually heterogeneous, and may represent uncertainty or clear statements about the contents of memory. A study examined the subjective intent of DK responses in relation to the objective status of information queried, in the context of memory distorting procedures. Participants viewed a video and responded to answerable and unanswerable questions phrased in misleading or nonmisleading formats, while hypnotized or not hypnotized. Subjective meanings of DK responses were queried, and a recognition measure assessed the contents of memory. Lower DK and accuracy rates were consistently associated with unanswerable and misleading questions. One-third of DK responses were statements that the information had no not presented. When these were recoded, accuracy estimates for answerable questions decreased and more so for hypnotized participants. These results demonstrate that DK responses convey different types of information, thus accuracy estimates in studies that permit DK responses may be misestimated. Robust risks associated with asking unanswerable questions and asking questions at all were observed. Implications for working with DK responses during interviews are discussed. PMID:18808279

  13. Effects of a Hypnotic Induction and an Unpleasantness-Focused Analgesia Suggestion on Pain Catastrophizing to an Experimental Heat Stimulus: A Preliminary Study.

    PubMed

    Adachi, Tomonori; Nakae, Aya; Sasaki, Jun

    2016-01-01

    Pain catastrophizing is associated with greater levels of pain. While many studies support the efficacy of hypnosis for pain, the effect on pain catastrophizing remains unclear. The present study evaluated the effect of hypnosis on pain catastrophizing using experimental heat stimulation. Twenty-two pain patients engaged in 3 conditions: baseline (no suggestion), hypnotic induction, and hypnotic induction plus analgesia suggestion. Participants with higher baseline pain showed a significant reduction in rumination following hypnotic induction plus analgesia suggestion and significant reductions in pain due to both the hypnotic induction alone and the hypnotic induction plus analgesia suggestion. The findings suggest that unpleasantness-focused hypnotic analgesia reduces pain via its effect on the rumination component of pain catastrophizing. PMID:27585727

  14. (1)H MRS in the rat brain under pentobarbital anesthesia: accurate quantification of in vivo spectra in the presence of propylene glycol.

    PubMed

    Iltis, Isabelle; Marjańska, Małgorzata; Du, Fei; Koski, Dee M; Zhu, Xiao-Hong; Ugurbil, Kâmil; Chen, Wei; Henry, Pierre-Gilles

    2008-03-01

    Commercial solutions for pentobarbital anesthesia typically contain water H spectra. The purpose of the present study was to measure the concentration of metabolites in the rat brain in vivo under pentobarbital anesthesia using 1H MRS. Resonances of PG, but not ethanol, were observed in the rat brain. Chemical shifts and J-coupling constants for PG were measured at 37 degrees C and pH 7.1 and used for spectral simulation. Inclusion of the simulated PG spectrum in the basis set for LCModel analysis enabled accurate fitting of in vivo spectra. This work demonstrates that concentration of brain metabolites can be reliably measured using 1H spectroscopy under pentobarbital anesthesia. The chemical shifts and J-coupling values reported here can be used to simulate the spectrum of PG at any field strength, with various pulse sequences. PMID:18224694

  15. Suppression of parasympathetic reflex vasodilatation in the lower lip of the cat by isoflurane, propofol, ketamine and pentobarbital: implications for mechanisms underlying the production of anaesthesia.

    PubMed

    Ito, Y; Izumi, H; Sato, M; Karita, K; Iwatsuki, N

    1998-10-01

    We have compared the effects of isoflurane, propofol, ketamine and pentobarbital on parasympathetic reflex vasodilatation to investigate their involvement in GABA-mediated synaptic inhibition, enhancement of which is thought to underlie the action of many anaesthetic agents. In cats anaesthetized with urethane-alpha-chloralose, parasympathetic reflex vasodilation in the ipsilateral lower lip was elicited by electrical stimulation of the central cut end of the lingual nerve. Isoflurane and pentobarbital both produced marked dose-dependent inhibition of this vasodilator response. In contrast, propofol and ketamine had no effect on parasympathetic reflex vasodilation. Administration of a GABA antagonist (picrotoxin) reversed the inhibition produced by isoflurane (previous results) and pentobarbital (present study). Our results suggest that isoflurane and pentobarbitone inhibit parasympathetic reflex vasodilatation via a GABA-mediated mechanism, but that propofol and ketamine have no such effect. Our results with propofol cast doubt on its presumed mechanism of action as an anaesthetic. PMID:9924233

  16. Pregnancy and pentobarbital anaesthesia modify hepatic synthesis of acylglycerol glycerol and glycogen from gluconeogenic precursors during fasting in rats.

    PubMed

    Zorzano, A; Herrera, E

    1988-12-01

    1. Incorporation of gluconeogenic precursors into blood glucose and hepatic glycogen and acylglycerol glycerol was examined in 24 h-fasted virgin rats by using a flooding procedure for substrate administration. At 10 min after their intravenous injection, the conversion of alanine or glycerol into liver glycogen or acylglycerol glycerol was proportional to glucose synthesis. 2. In 24 h-fasted 21-day-pregnant rats, the incorporation of alanine and glycerol into hepatic acylglycerol glycerol was markedly enhanced compared with the control group. In addition, during fasting at late pregnancy, the proportion of substrates directed to acylglycerol glycerol as compared with the fraction incorporated into glucose was augmented. 3. In pentobarbital-treated fasted rats, the incorporation of both alanine and pyruvate into circulating glucose and into hepatic glycogen and acylglycerol glycerol was increased. Pentobarbital treatment increased the proportion of substrates incorporated into liver glycogen, compared with the fraction appearing in circulating glucose. These changes were concomitant with a marked accumulation of glycogen. 4. The data indicate that, during fasting, gluconeogenesis provides glucose as well as hepatic glycogen and acylglycerol glycerol, independently of whether the substrates enter gluconeogenesis at the level of pyruvate or dihydroxyacetone phosphate. PMID:3223926

  17. Imperceptible signs: remnants of magnétisme in scientific discourses on hypnotism in late nineteenth-century France.

    PubMed

    Hajek, Kim M

    2015-01-01

    In 1880s France, hypnotism enjoyed unique medico-scientific legitimacy. This was in striking contrast to preceding decades when its precursor, magnétisme animal, was rejected by the medical/academic establishment as a disreputable, supernaturally tinged practice. Did the legitimation of hypnotism result from researchers repudiating any reference to the wondrous? Or did strands of magnetic thinking persist? This article interrogates the relations among hypnotism, magnétisme, and the domain of the wondrous through close analysis of scientific texts on hypnotism. In question is the notion that somnambulist subjects possessed hyperacute senses, enabling them to perceive usually imperceptible signs, and thus inadvertently to denature researchers' experiments (a phenomenon known as unconscious suggestion). The article explores researchers' uncritical and unanimous acceptance of these ideas, arguing that they originate in a holdover from magnétisme. This complicates our understanding of the continuities and discontinuities between science and a precursor "pseudo-science," and, more narrowly, of the notorious Salpêtrière-Nancy "battle" over hypnotism. PMID:26362719

  18. NEUROPEPTIDE MODULATION OF CHEMICALLY INDUCED SKIN IRRITATION

    EPA Science Inventory

    This study was designed to demonstrate that the early symptoms of chemically-induced skin irritation are neurally mediated. everal approaches were used to affect nerve transmission in adult Balb/c female mice. hese included general anesthesia (i.e., sodium pentobarbital), systemi...

  19. Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study

    PubMed Central

    Pearce, Hannah Louise; Croft, Peter; Singh, Swaran; Crome, Ilana; Bashford, James; Frisher, Martin

    2014-01-01

    Objective To test the hypothesis that people taking anxiolytic and hypnotic drugs are at increased risk of premature mortality, using primary care prescription records and after adjusting for a wide range of potential confounders. Design Retrospective cohort study. Setting 273 UK primary care practices contributing data to the General Practice Research Database. Participants 34 727 patients aged 16 years and older first prescribed anxiolytic or hypnotic drugs, or both, between 1998 and 2001, and 69 418 patients with no prescriptions for such drugs (controls) matched by age, sex, and practice. Patients were followed-up for a mean of 7.6 years (range 0.1-13.4 years). Main outcome All cause mortality ascertained from practice records. Results Physical and psychiatric comorbidities and prescribing of non-study drugs were significantly more prevalent among those prescribed study drugs than among controls. The age adjusted hazard ratio for mortality during the whole follow-up period for use of any study drug in the first year after recruitment was 3.46 (95% confidence interval 3.34 to 3.59) and 3.32 (3.19 to 3.45) after adjusting for other potential confounders. Dose-response associations were found for all three classes of study drugs (benzodiazepines, Z drugs (zaleplon, zolpidem, and zopiclone), and other drugs). After excluding deaths in the first year, there were approximately four excess deaths linked to drug use per 100 people followed for an average of 7.6 years after their first prescription. Conclusions In this large cohort of patients attending UK primary care, anxiolytic and hypnotic drugs were associated with significantly increased risk of mortality over a seven year period, after adjusting for a range of potential confounders. As with all observational findings, however, these results are prone to bias arising from unmeasured and residual confounding. PMID:24647164

  20. A single dose of hypnotic corrects sleep and EEG abnormalities in symptomatic Huntington's disease mice.

    PubMed

    Kantor, Sandor; Varga, Janos; Morton, A Jennifer

    2016-06-01

    Sleep and electroencephalogram abnormalities are prominent early features of Huntington's disease (HD) that typically appear before the onset of characteristic motor symptoms. The changes in sleep and electroencephalogram seen in HD patients are largely recapitulated in mouse models of HD such as transgenic R6/2 lines. To test whether or not drugs with hypnotic properties can correct the sleep and electroencephalogram abnormalities seen in HD mice, we treated male wild-type (WT; N = 7) and R6/2 mice (N = 9) acutely with intraperitoneal injections of vehicle, zolpidem (5, 10 or 20 mg/kg) or amitriptyline (5, 10 or 20 mg/kg), and then monitored their sleep-wake behavior. In R6/2 mice, both zolpidem and amitriptyline suppressed the abnormally high REM sleep amount and electroencephalographic gamma (30-46 Hz) oscillations in a dose-dependent manner. Amitriptyline's effect on sleep was similar in both genotypes, whereas zolpidem showed significant genotype differences. Zolpidem exerted a strong hypnotic effect in WT mice by increasing electroencephalographic delta power, doubling the mean bout duration and the total amount of non-rapid eye movement sleep. However, no such effect was seen in R6/2 mice. Our study demonstrates that the pathophysiological changes seen in sleep and electroencephalogram are not 'hard-wired' in HD brain and can be reversed even at late stages of the disease. The diminished hypnotic effect of zolpidem suggests that the GABAergic control of sleep-wake states is impaired in HD mice. A better understanding of the neurochemical basis underlying these abnormalities should lead to more effective and rational therapies for HD. PMID:26805423

  1. EFFECT OF OZONE ON DRUG-INDUCED SLEEPING TIME IN MICE PRETREATED WITH MIXED-FUNCTION OXIDASE INDUCERS AND INHIBITORS

    EPA Science Inventory

    Studies were conducted to investigate the effect of ozone in prolonging pentobarbital (PEN)-induced sleeping time (S.T.). Since ozone is a common air pollutant, an ozone-induced alteration of mechanisms of drug action could have public health implications. It was shown that a 5-h...

  2. Hypnotic induction is followed by state-like changes in the organization of EEG functional connectivity in the theta and beta frequency bands in high-hypnotically susceptible individuals

    PubMed Central

    Jamieson, Graham A.; Burgess, Adrian P.

    2014-01-01

    Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information) between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs) and 11 low susceptible (lows) participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH) and the imaginary component of coherence (iCOH), which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1–3.9 Hz), theta (4–7.9 Hz) alpha (8–12.9 Hz), beta1 (13–19.9 Hz), beta2 (20–29.9 Hz) and gamma (30–45 Hz). The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized “hypnotic-state.” PMID:25104928

  3. Hypnotic intervention in a 7-year-old thumbsucker: a case study.

    PubMed

    Grayson, David N

    2012-01-01

    Thumbsucking is a common habit among younger children. Usually, the child outgrows this habit by age 6. When a child over the age of 6 continues to suck his or her thumb, it can be a cause of potential harm due to peer pressure, ridicule, and shunning. It can also lead to malocclusions requiring eventual orthodontic interventions. In this case study, the author demonstrates a hypnotic intervention in a 7-year-old girl. Validation of her habit and imaging a role model sucking her thumb were employed in trance. Using this approach, the child was able to end her dependence on thumbsucking in 1 session. PMID:22443022

  4. Hypnotizability and opinions about hypnosis in a clinical trial for the hypnotic control of pain and anxiety during pregnancy termination.

    PubMed

    Dufresne, Alexandra; Rainville, Pierre; Dodin, Sylvie; Barré, Patrick; Masse, Benoît; Verreault, René; Marc, Isabelle

    2010-01-01

    This descriptive study evaluates the hypnoanalgesic experience's effect on participants' hypnotizability and opinions about hypnosis and identifies factors associated with hypnotizability. Hypnotizability was assessed using the Stanford Hypnotic Susceptibility Scale: Form A in 290 women 1 month after their participation in a randomized clinical trial evaluating hypnotic intervention for pain/anxiety versus standard care during pregnancy termination. Opinions were collected before and after the intervention. The regression model describing hypnotizability (F = 13.55; p < .0001; R(2) = 0.20) retained 5 variables but not the intervention group. The variable explaining most of total variance (62.9%) was the level of perceived automaticity/involuntariness. Opinions about hypnosis were modified by the hypnotic experience compared to standard care but were not associated with hypnotizability. Exposure to hypnoanalgesia did not influence hypnotizability but modifies significantly the opinions about hypnosis. Consistent with previous findings, perceived automaticity appears to best predict hypnotizability. PMID:20183740

  5. Observed differences in learning ability of heart rate self-regulation as a function of hypnotic susceptibility

    NASA Technical Reports Server (NTRS)

    Cowings, P. S.

    1977-01-01

    Three groups of eight male and female subjects (aged 20-27 yr) categorized by low and high hypnotic susceptibility were taught to control their heart rates by means of an appropriate autogenic therapy/biofeedback technique. The experimental groups were trained by autogenic therapy and biofeedback, while the control group received only biofeedback. Significant differences are observed in all psychological test scores between subjects of high and low hypnotic susceptibility. The results confirm that (1) there are qualitative and quantitative differences between the performance of individuals with high and low hypnotic susceptibility; (2) interindividual-variability tests yield data relevant to individual performance in visceral learning tasks; (3) the combined autogenic therapy/biofeedback/verbal feedback technique is suitable for conditioning large stable autonomic responses in humans; and (4) this kind of conditioning is effective in eliminating or alleviating physiological reactions to some environmental stressors.

  6. Perceiving Time Differences When You Should Not: Applying the El Greco Fallacy to Hypnotic Time Distortions.

    PubMed

    Martin, Jean-Rémy; Sackur, Jérôme; Anlló, Hernan; Naish, Peter; Dienes, Zoltan

    2016-01-01

    The way we experience and estimate time - subjective time - does not systematically correspond to objective time (the physical duration of an event). Many factors can influence subjective time and lead to mental dilation or compression of objective time. The emotional valence of stimuli or the levels of attention or expectancy are known to modulate subjective time even though objective time is constant. Hypnosis too is known to alter people's perception of time. However, it is not known whether hypnotic time distortions are intrinsic perceptual effects, based for example on the changing rate of an internal clock, or rather the result of a response to demand characteristics. Here we distinguished the theories using the logic of the El Greco fallacy. When participants initially had to compare the duration of two successive events -with the same duration - while in "trance," they responded that the second event was on average longer than the first event. As both events were estimated in "trance," if hypnosis had impacted on an internal clock, they should have been affected to the same extent. Conversely, when only the first event was in "trance," there was no difference in perceived duration. The findings conform to an El Greco fallacy effect and challenge theories of hypnotic time distortion arguing that "trance" itself changes subjective time. PMID:27625623

  7. Perceiving Time Differences When You Should Not: Applying the El Greco Fallacy to Hypnotic Time Distortions

    PubMed Central

    Martin, Jean-Rémy; Sackur, Jérôme; Anlló, Hernan; Naish, Peter; Dienes, Zoltan

    2016-01-01

    The way we experience and estimate time – subjective time – does not systematically correspond to objective time (the physical duration of an event). Many factors can influence subjective time and lead to mental dilation or compression of objective time. The emotional valence of stimuli or the levels of attention or expectancy are known to modulate subjective time even though objective time is constant. Hypnosis too is known to alter people’s perception of time. However, it is not known whether hypnotic time distortions are intrinsic perceptual effects, based for example on the changing rate of an internal clock, or rather the result of a response to demand characteristics. Here we distinguished the theories using the logic of the El Greco fallacy. When participants initially had to compare the duration of two successive events —with the same duration — while in “trance,” they responded that the second event was on average longer than the first event. As both events were estimated in “trance,” if hypnosis had impacted on an internal clock, they should have been affected to the same extent. Conversely, when only the first event was in “trance,” there was no difference in perceived duration. The findings conform to an El Greco fallacy effect and challenge theories of hypnotic time distortion arguing that “trance” itself changes subjective time. PMID:27625623

  8. Hypnotic Seminar.

    PubMed

    Haley, Jay

    2015-01-01

    In this transcription of a lecture given in 2000, Jay Haley begins by answering the question, "What is hypnosis?"  Haley reviews the circumstances of Gregory Bateson encouraging him to meet with Milton Erickson to discuss the history of hypnosis and the paradoxical nature of trance induction. Haley expresses many original thoughts about multiple personalities, regression to past lives, and how to handle memories that historically may be false. Sophisticated and subtle, this is Haley at his best. PMID:26305134

  9. Evaluating hypnotic memory enhancement (hypermnesia and reminiscence) using multitrial forced recall.

    PubMed

    Dinges, D F; Whitehouse, W G; Orne, E C; Powell, J W; Orne, M T; Erdelyi, M H

    1992-09-01

    Two experiments investigated whether hypnosis enhances memory retrieval per se or merely increases a person's willingness to report recollections. Both experiments assessed immediate and delayed (i.e., 1 week) recall for pictorial stimuli. In Experiment 1, following an initial waking baseline recall, subjects of high or low hypnotic ability completed a series of recall trials conducted either in hypnosis or in the walking condition. The classic hypermnesia effect was obtained, but with no supplemental contribution of hypnosis. In Experiment 2, hypnosis was introduced only after 6 waking-recall trials. Hypnosis again failed to enhance retrieval of new correct items, although it increased the production of new incorrect recall among hypnotizable individuals. The findings provide no evidence for alleged hypermnesic properties of hypnosis. PMID:1402714

  10. Hypnotically assisted diaphragmatic exercises in the treatment of stuttering: a preliminary investigation.

    PubMed

    Kaya, Yalcin; Alladin, Assen

    2012-01-01

    This preliminary study investigates the combined effect of intensive hypnotherapy and diaphragmatic exercises in the management of stuttering. Fifty-nine clients with stuttering were trained to practice abdominal weightlifting to strengthen their respiratory muscles and to improve their diaphragmatic movements. The weightlifting exercises involved lifting a dumbbell (2.0-4.0 kg) with the abdomen for 2 hours daily for 8 consecutive days. Hypnotherapy was utilized to alleviate anxiety, to boost self-confidence, and to increase motivation for weightlifting exercise. The pre- and postmeasures were statistically significant (p < .001). Results of the study provide support for the effectiveness of hypnotically assisted diaphragmatic training in the management of stuttering but should be further studied in controlled trials. PMID:22443525

  11. Conscious/Unconscious Dissociation Induction: Increasing Hypnotic Performance With "Resistant" Clients.

    PubMed

    Lankton, Stephen

    2016-10-01

    Milton H. Erickson promoted several approaches to psychotherapy using hypnosis. In the last decades of his life, his work moved away from the use of redundant suggestion and a predominance of direct suggestion in favor of indirect suggestion. In addition, he frequently employed a type of storytelling (that has come to be called therapeutic metaphor) to indirectly convey learning. Another change that occurred during the last decade was his definition of the cause of a symptom. However, there were two important areas of his work that he did not change during his career. These two components of his work he did not change were his definition of a cure and the importance of a naturalistic induction. This article concerns his naturalistic approach to hypnotic induction and especially his use of conscious/unconscious dissociation in the induction process and how indirect suggestion and therapeutic binds can be used to facilitate that type of induction and a cure. PMID:27586046

  12. Use of Neurofeedback to Enhance Response to Hypnotic Analgesia in Individuals With Multiple Sclerosis.

    PubMed

    Jensen, Mark P; Gianas, Ann; George, Holly R; Sherlin, Leslie H; Kraft, George H; Ehde, Dawn M

    2016-01-01

    This proof of principle study examined the potential benefits of EEG neurofeedback for increasing responsiveness to self-hypnosis training for chronic pain management. The study comprised 20 individuals with multiple sclerosis (MS) who received 5 sessions of self-hypnosis training--1 face-to-face session and 4 prerecorded sessions. Participants were randomly assigned to have the prerecorded sessions preceded by either (a) EEG biofeedback (neurofeedback) training to increase left anterior theta power (NF-HYP) or (b) a relaxation control condition (RLX-HYP). Eighteen participants completed all treatment sessions and assessments. NF-HYP participants reported greater reductions in pain than RLX-HYP participants. The findings provide support for the potential treatment-enhancing effects of neurofeedback on hypnotic analgesia and also suggest that effective hypnosis treatment can be provided very efficiently. PMID:26599991

  13. The center core in ego state therapy and other hypnotically facilitated psychotherapies.

    PubMed

    Frederick, Claire

    2013-07-01

    Center core phenomena have been utilized in the practice of ego state therapy and other forms of hypnotically facilitated psychotherapy for nearly 40 years. Despite the frequency with which they are employed, many confusions, contradictions, and questions remain concerning them. In this article relevant center core phenomena literature is reviewed and an essential differentiation between two different kinds of center core phenomena is clarified. Psychodynamic explanations are offered for the therapeutic benefits of archetypal center core experiences such as inner strength and inner wisdom. The information provided offers clinicians a sturdier platform from which to decide whether to incorporate center core experiences into clinical practice. The persistent question of whether center core phenomena are ego states is revisited and addressed. PMID:24660338

  14. [Attitude and perceived control of the elderly towards the consumption of anxiolytic, sedative and hypnotic medications].

    PubMed

    Guindon, Marilyn; Cappeliez, Philippe

    2011-03-01

    This study examines the importance of variables from the Theory of Planned Behaviour (i.e., attitudes toward behaviour, subjective norms, and perceived control) for the prediction of consumption of anxiolytic and sedative-hypnotic (ASH) medications in a sample of older persons, aged 69 years on average, 62 consumers and 92 non-consumers. A favourable attitude toward ASH and a sense of having less control regarding these drugs predict both current usage and intention to continue. Perceived control predicts intention to start consumption of ASH in current non-consumers. This study underlines the importance of considering the role of the older person's decisional power in the consumption of these medications. PMID:21470438

  15. Hypnotic analgesia for combat-related spinal cord injury pain: a case study.

    PubMed

    Stoelb, Brenda L; Jensen, Mark P; Tackett, M Jan

    2009-01-01

    A U.S. Army soldier stationed in Iraq developed myriad pain problems after sustaining a high-level spinal cord injury (SCI) from a gunshot wound. These problems were negatively impacting his ability to participate fully in his physical rehabilitation and care. Ten sessions of self-hypnosis training were administered to the patient over a 5-week period to help him address these problems. Both the patient and his occupational therapist reported a substantial reduction in pain over the course of treatment, which allowed the patient to actively engage in his therapies. Six months post treatment, the patient reported continued use of the hypnosis strategies taught, which effectively reduced his experience of pain. This case study demonstrates the efficacy of hypnotic analgesia treatment for U.S. military veterans who are experiencing pain problems due to traumatic or combat-related SCIs. PMID:19216212

  16. Seeing Blue As Red: A Hypnotic Suggestion Can Alter Visual Awareness of Colors.

    PubMed

    Kallio, Sakari; Koivisto, Mika

    2016-01-01

    Some highly hypnotizable individuals have reported changes in objects' color with suggestions given in normal waking state. However, it is not clear whether this occurs only in their imagination. The authors show that, although subjects could imagine colors, a posthypnotic suggestion was necessary for seeing altered colors, even for a hypnotic virtuoso. She reported posthypnotic color alterations also selectively in response to specific target shapes in briefly presented object arrays. Surprisingly, another highly hypnotizable person showed a very different pattern of results. The control participants could not simulate virtuosos' results by applying cognitive strategies. The results imply that hypnosis can alter the functioning of automatic visual processes but only in some of the most hypnotizable individuals. PMID:27267673

  17. The Importance of Residual Effects When Choosing a Hypnotic: The Unique Profile of Zaleplon.

    PubMed

    Zammit, Gary K.; Kramer, Jeffrey A.

    2001-04-01

    BACKGROUND: Insomnia is a prevalent medical disorder that has significant effects on occupational performance, health, and quality of life. Insomnia places an enormous burden on society through increased visits to physicians, loss of productivity in the workplace, and an increased rate of accidents. An estimated sum of $100 million is spent each year on direct treatment of unresolved insomnia. Physicians need to initiate early effective treatment to prevent development of chronic insomnia and its associated morbidity. Institution of good sleep hygiene practices may be useful in some patients but may not be adequate for resolution of all sleep problems. Behavioral treatments, while effective and durable, are time consuming and not widely utilized in clinical practice. Pharmacotherapy includes benzodiazepine hypnotics, but concerns regarding adverse effects (e.g., residual sedation) prompted the search for safer options. DATA SOURCES: Published and presented studies containing clinical data on zaleplon, a new nonbenzodiazepine sleep medication, were identified via MEDLINE, Current Contents (ISI database), bibliographic reviews, and consultation with sleep specialists. RESULTS: Zaleplon effectively shortens sleep onset time and improves the quality of sleep in patients with insomnia. Whether administered at bedtime or later at night, zaleplon is devoid of residual sedative effects that impair next-day functioning. Follow-up studies evaluating the long-term efficacy and safety of zaleplon showed that decreased time to sleep onset was maintained during therapy lasting up to 52 weeks, without a withdrawal syndrome after discontinuation. CONCLUSION: Insomnia is recurrent and unpredictable in nature. Despite the long-term morbidity of this sleep disorder, research evidence and practice guidelines have not explored long-term use of hypnotics. Many patients could benefit from long-term drug therapy with a sleep medication that is devoid of residual effects and can be taken

  18. Sedative and hypnotic drugs--fatal and non-fatal reference blood concentrations.

    PubMed

    Jönsson, Anna Kristina; Söderberg, Carl; Espnes, Ketil Arne; Ahlner, Johan; Eriksson, Anders; Reis, Margareta; Druid, Henrik

    2014-03-01

    In postmortem investigations of fatal intoxications it is often challenging to determine which drug/s caused the death. To improve the interpretation of postmortem blood concentrations of sedative and hypnotic drugs and/or clonazepam, all medico-legal autopsies in Sweden - where these drugs had been detected in femoral vein blood during 1992-2006 - were identified in the databases of the National Board of Forensic Medicine. For each drug, concentrations in postmortem control cases - where the cause of death was not intoxication and where incapacitation by drugs could be excluded - were compiled as well as the levels found in living subjects; drugged driving cases and therapeutic drug monitoring cases. Subsequently, fatal intoxications were assessed with regards to the primary substances contributing to death, and blood levels were compiled for single and multiple drug intoxications. The postmortem femoral blood levels are reported for 16 sedative and hypnotic drugs, based on findings in 3560 autopsy cases. The cases were classified as single substance intoxications (N=498), multiple substance intoxications (N=1555) and postmortem controls (N=1507). Each autopsy case could be represented more than once in the group of multiple intoxications and among the postmortem controls if more than one of the included substances were detected. The concentration ranges for all groups are provided. Overlap in concentrations between fatal intoxications and reference groups was seen for most substances. However, the concentrations found in single and multiple intoxications were significantly higher than concentrations found in postmortem controls for all substances except alprazolam and triazolam. Concentrations observed among drugged drivers were similar to the concentrations observed among the therapeutic drug monitoring cases. Flunitrazepam was the substance with the highest number of single intoxications, when related to sales. In summary, this study provides reference drug

  19. Functional sites involved in modulation of the GABAA receptor channel by the intravenous anesthetics propofol, etomidate and pentobarbital.

    PubMed

    Maldifassi, Maria C; Baur, Roland; Sigel, Erwin

    2016-06-01

    GABAA receptors are the major inhibitory neurotransmitter receptors in the brain and are the target for many clinically important drugs. Among the many modulatory compounds are also the intravenous anesthetics propofol and etomidate, and barbiturates. The mechanism of receptor modulation by these compounds is of mayor relevance. The site of action of these compounds has been located to subunit interfaces in the intra-membrane region of the receptor. In α1β2γ2 GABAA receptors there are five such interfaces, two β+/α- and one each of α+/β-, α+/γ- and γ+/β- subunit interfaces. We have used reporter mutations located in the second trans-membrane region in different subunits to probe the effects of changes at these subunit interfaces on modulation by propofol, etomidate and pentobarbital. We provide evidence for the fact that each of these compounds either modulates through a different set of subunit interfaces or through the same set of subunit interfaces to a different degree. As a GABAA receptor pentamer harbors two β+/α- subunit interfaces, we used concatenated receptors to dissect the contribution of individual interfaces and show that only one of these interfaces is important for receptor modulation by etomidate. PMID:26767954

  20. Liquid chromatography/mass spectrometry for timely response in regulatory analyses: identification of pentobarbital in dog food.

    PubMed

    Heller, D N

    2000-07-01

    A limited liquid chromatography/mass spectrometry (LC/ MS) data set was acquired under conditions which called for timely response without benefit of a fully developed method. Quality assurance elements verified that an LC/ MS procedure developed in a short-time was sufficiently under control to meet its purpose. LC/MS was used to rule out a potential problem with a gas chromatography (GC)/MS method that had been developed for regulatory purposes. The LC/MS data set showed that signals identified by GC/MS as diagnostic of pentobarbital (PB) were not artifacts of derivatization or GC analysis. Samples of dry dog food identified by GC/MS as containing PB were also shown by LC/MS to contain PB. The LC/MS method would not be recommended as a substitute for GC/MS, primarily because of poorer sensitivity. Although the data set is limited, and justifiably represents only the starting point for conventional method development, the purpose at hand was served adequately. This work demonstrates the utility of LC/MS for rapid regulatory response, provided there is a framework of quality assurance checks. PMID:10905297

  1. Crime, hysteria and belle époque hypnotism: the path traced by Jean-Martin Charcot and Georges Gilles de la Tourette.

    PubMed

    Bogousslavsky, Julien; Walusinski, Olivier; Veyrunes, Denis

    2009-01-01

    Hysteria and hypnotism became a favorite topic of studies in the fin de siècle neurology that emerged from the school organized at La Salpêtrière by Jean-Martin Charcot, where he had arrived in 1861. Georges Gilles de la Tourette started working with Charcot in 1884 and probably remained his most faithful student, even after his mentor's death in 1893. This collaboration was particularly intense on 'criminal hypnotism', an issue on which Hippolyte Bernheim and his colleagues from the Nancy School challenged the positions taken by the Salpêtrière School. Bernheim claimed that hypnotism was not a diagnostic feature of hysteria and that there were real-life examples of murders suggested under hypnosis, while hypnosis susceptibility was identified with hysteria by Charcot and Gilles de la Tourette, who saw rape as the only crime associated with hypnotism. The quarrel was particularly virulent during a series of famous criminal cases which took place between 1888 and 1890. At the time, it was considered that La Salpêtrière had succeeded over Nancy, since the role of hypnotism was discarded during these famous trials. However, the theories of Charcot and Gilles de la Tourette were also damaged by the fight, which probably triggered the conceptual evolution leading to Joseph Babinski's revision of hysteria in 1901. Gilles de la Tourette's strong and public interest in hypnotism nearly cost him his life, when a young woman who claimed to have been hypnotized against her will shot him in the head at his own home in 1893. It was subsequently shown that hypnotism had nothing to do with it. The delusional woman was interned at Sainte-Anne for mental disturbance, thus escaping trial. Ironically, Gilles de la Tourette may have been partly responsible, since he had been one of the strongest proponents of placing mentally-ill criminals in asylums instead of prisons. PMID:19602893

  2. Zolpidem induced hyponatremia: a case report.

    PubMed

    Priya S, Shanmuga; Dl, Britto; T, Saravanan

    2014-09-01

    Zolpidem is a non-benzodiazepine hypnotic that acts by binding to (GABAA) receptor. This is a case report of a patient with chronic insomnia for which he had initially been receiving benzodiazepine hypnotic alprazolam and for the past three years, he had switched himself to non-benzodiazepine hypnotic, zolpidem and had progressively increased the dose to 20 mg. The patient presented with history of drowsiness, nausea and vomiting of short duration. Investigations revealed that the patient had hyponatremia. Decreased serum sodium, elevated urine sodium with normal urine osmolarity was detected. Therefore, we report this as a case of drug induced syndrome of inappropriate antidiuretic hormone (SIADH) as other likely causes were ruled out by appropriate investigations. The causality assessment was done according to the WHO scale and found to be "Probable". PMID:25386461

  3. Visual field asymmetry in facial affect perception: moderating effects of hypnosis, hypnotic susceptibility level, absorption, and sustained attentional abilities.

    PubMed

    Crawford, H J; Harrison, D W; Kapelis, L

    1995-05-01

    Effects of hypnotic level, affect valence and cerebral asymmetry on reaction time (RT) in the discrimination of Ekman and Friesen's (1978) stimuli of angry and happy faces were studied in counterbalanced conditions of waking and hypnosis. Assessed previously on two hypnotic susceptibility scales [Harvard Group Scale of Hypnotic Susceptibility; Stanford Hypnotic Susceptibility Scale, Form C (SHSSC)], non-depressed subjects were 16 low (0-4 SHSSC) and 17 highly (10-12 SHSSC) hypnotizable, right-handed college students. Subjects were required to identify affects of faces, presented tachistoscopically to left (LVF) or right (RVF) visual fields, by using a forced-choice RT paradigm. Highs were significantly faster than lows in angry and happy affect recognition. Hypnosis had no significant effects. For highs only, angry emotional valence was identified faster when presented to the right hemisphere (LVF), but there were no significant hemispheric effects for happy emotional valence. For lows there were no hemispheric differences. Gender was a nonsignificant factor. Significant correlations showed that faster reaction times to angry and happy stimuli, in both LVF and RVF in waking and hypnosis, were obtained by subjects who reported more deeply absorbed and extremely focused and sustained attention on the Tellegen (1982) Absorption Scale and a subscale of the Differential Attentional Processes Inventory (Grumbles & Crawford, 1981). Vividness of Visual Imagery Questionnaire (Marks, 1973) and Affect Intensity Measure (Larsen, 1985), in general, did not correlate with RTs. The potential role of the fronto-limbic attentional system in the recognition of external visual sensory affect is discussed. PMID:7591508

  4. Abrupt changes in pentobarbital sensitivity in preBötzinger complex region, hypoglossal motor nucleus, nucleus tractus solitariius, and cortex during rat transitional period (P10–P15)

    PubMed Central

    Turner, Sara M. F.; Johnson, Stephen M.

    2015-01-01

    On postnatal days P10–P15 in rat medulla, neurotransmitter receptor subunit composition shifts towards a more mature phenotype. Since medullary GABAARs regulate cardiorespiratory function, abrupt alterations in GABAergic synaptic inhibition could disrupt homeostasis. We hypothesized that GABAARs on medullary neurons become more resistant to positive allosteric modulation during P10–P15. Medullary and cortical slices from P10–P20 rats were used to record spontaneous action potentials in pre-Botzinger Complex (preBötC-region), hypoglossal (XII) motor nucleus, nucleus tractus solitariius (NTS), and cortex during exposure to pentobarbital (positive allosteric modulator of GABAARs). On P14, pentobarbital resistance abruptly increased in preBötC-region and decreased in NTS, but these changes in pentobarbital resistance were not present on P15. Pentobarbital resistance decreased in XII motor nucleus during P11–P15 with a nadir at P14. Abrupt changes in pentobarbital resistance indicate changes in GABAergic receptor composition and function that may compensate for potential increased GABAergic inhibition and respiratory depression that occurs during this key developmental transitional period. PMID:25550216

  5. Effect of hypnotic suggestion on fibromyalgic pain: comparison between hypnosis and relaxation.

    PubMed

    Castel, Antoni; Pérez, Magdalena; Sala, José; Padrol, Anna; Rull, Maria

    2007-05-01

    The main aims of this experimental study are: (1) to compare the relative effects of analgesia suggestions and relaxation suggestions on clinical pain, and (2) to compare the relative effect of relaxation suggestions when they are presented as "hypnosis" and as "relaxation training". Forty-five patients with fibromyalgia were randomly assigned to one of the following experimental conditions: (a) hypnosis with relaxation suggestions; (b) hypnosis with analgesia suggestions; (c) relaxation. Before and after the experimental session, the pain intensity was measured using a visual analogue scale (VAS) and the sensory and affective dimensions were measured with the McGill Pain Questionnaire. The results showed: (1) that hypnosis followed by analgesia suggestions has a greater effect on the intensity of pain and on the sensory dimension of pain than hypnosis followed by relaxation suggestions; (2) that the effect of hypnosis followed by relaxation suggestions is not greater than relaxation. We discuss the implications of the study on our understanding of the importance of suggestions used in hypnosis and of the differences and similarities between hypnotic relaxation and relaxation training. PMID:16889999

  6. Effects of different cyclodextrins on the morphology, loading and release properties of poly (DL-lactide-co-glycolide)-microparticles containing the hypnotic agent etizolam.

    PubMed

    Lopedota, A; Cutrignelli, A; Trapani, A; Boghetich, G; Denora, N; Laquintana, V; Trapani, G; Liso, G

    2007-05-01

    The aim of this study was to gain insight into the feasibility of using microparticles (MPs) constituted by the biodegradable poly (DL-lactide-co-glycolide) (PLGA) and a number of cyclodextrins (CDs) as an orally sustained delivery system of the hypnotic agent etizolam (ETZ). A further aim of the work was to investigate the effects of different CDs on the morphology, loading, and release properties of the MPs prepared. For these purposes, ETZ alone, and ETZ/CD-PLGA loaded MPs were prepared by the W/O/W emulsion-solvent evaporation method. It was found that the release of ETZ in vitro was more prolonged over three days with a kinetic constant proportional to t(1/2). It was also demonstrated that the CDs in these MPs are able to modulate several properties such as morphology, drug loading, and release properties. In fact, marked differences in shape, surface, and encapsulation efficiencies were noted depending on the presence, hydrophilicity, and charge of the CD employed. The obtained results induce us to consider the present ETZ-containing formulations as new valuable tools for the treatment of different insomnia categories. PMID:17454433

  7. Hypnotics and the Occurrence of Bone Fractures in Hospitalized Dementia Patients: A Matched Case-Control Study Using a National Inpatient Database

    PubMed Central

    Tamiya, Hiroyuki; Yasunaga, Hideo; Matusi, Hiroki; Fushimi, Kiyohide; Ogawa, Sumito; Akishita, Masahiro

    2015-01-01

    Background Preventing falls and bone fractures in hospital care is an important issue in geriatric medicine. Use of hypnotics is a potential risk factor for falls and bone fractures in older patients. However, data are lacking on the association between use of hypnotics and the occurrence of bone fracture. Methods We used a national inpatient database including 1,057 hospitals in Japan and included dementia patients aged 50 years or older who were hospitalized during a period of 12 months between April 2012 and March 2013. The primary outcome was the occurrence of bone fracture during hospitalization. Use of hypnotics was compared between patients with and without bone fracture in this matched case-control study. Results Of 140,494 patients, 830 patients suffered from in-hospital fracture. A 1:4 matching with age, sex and hospital created 817 cases with fracture and 3,158 matched patients without fracture. With adjustment for the Charlson comorbidity index, emergent admission, activities of daily living, and scores for level walking, a higher occurrence of fractures were seen with short-acting benzodiazepine hypnotics (odds ratio, 1.43; 95% confidence interval, 1.19–1.73; P<0.001), ultrashort-acting non-benzodiazepine hypnotics (1.66; 1.37–2.01; P<0.001), hydroxyzine (1.45; 1.15–1.82, P=0.001), risperidone and perospirone (1.37; 1.08–1.73; P=0.010). Other drug groups were not significantly associated with the occurrence of in-hospital fracture. Conclusions Short-acting benzodiazepine hypnotics and ultrashort-acting non-benzodiazepine hypnotics may increase risk of bone fracture in hospitalized dementia patients. PMID:26061231

  8. Effect of pentobarbital anaesthesia on intestinal absorption and hepatic first-pass metabolism of oxacillin in rats, evaluated by portal-systemic concentration difference.

    PubMed

    Ueda, S; Yamaoka, K; Nakagawa, T

    1999-05-01

    The effects of anaesthesia on intestinal drug absorption and hepatic first-pass metabolism in rats were investigated by observing the difference in the drug concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra-arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra-arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin concentrations in plasma were assayed by HPLC. The anaesthesia increased the absolute bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (F(H)), but caused little change in the local absorption ratio into the portal system (Fa) and the total clearance (CL). The hepatic clearance (CL(H)) was significantly decreased, resulting in an apparent small change in CL-CL(H) which is considered to be renal clearance. By this method, it was shown directly that an increase in F due to pentobarbital anaesthesia was attributable to the significant increase in F(H). It is expected that the method is useful not only to evaluate the effect of anaesthesia on the first-pass effect, but also to assess the effect of co-administration of drugs on first-pass metabolism. PMID:10411218

  9. Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline.

    PubMed

    Woolverton, W L; Nader, M A

    1995-12-01

    The purpose of the present study was to further investigate the relationship between the DS effects of PB and those of benzodiazepines (BZs) and to begin to collect pharmacological information concerning receptor mechanisms involved in this behavioral effect of BZs. Rhesus monkeys (n = 3), trained to discriminate pentobarbital (PB; 10 mg/kg, IG) from saline under a discrete-trials shock avoidance procedure, were given IG diazepam (0.3-10 mg/kg), chlordiazepoxide (1.0-30 mg/kg), or etizolam (0.3-10 mg/kg) alone and in combination with flumazenil (0.01-1.7 mg/kg, IM). Flumazenil was administered 10 min prior to the administration of saline, PB or the BZs. All three BZs fully substituted for PB in all monkeys. Diazepam was the most potent with a mean ED50 of 0.81 mg/kg (SEM = 0.04) while chlordiazepoxide was the least potent (mean ED50 = 5.78 mg/kg, SEM = 1.22 mg/kg). The ED50 for etizolam was 1.22 mg/kg (SEM = 0.37 mg/kg). Pretreatment with flumazenil (0.01-1.0 mg/kg) resulted in a dose-related parallel shift to the right in the dose-response function for PB-appropriate responding in all monkeys for all three BZs. The mean (n = 3) pKB value with 0.1 mg/kg flumazenil was 6.51 (SEM = 0.42) for diazepam and 6.57 (SEM = 0.17) for chlordiazepoxide. This value could not be calculated for etizolam because only one monkey was tested with 0.1 mg/kg flumazenil. However, the mean pKB for etizolam considering all monkeys and all doses of flumazenil was 6.58 (SEM = 0.47). Apparent pA2 values for flumazenil with diazepam were 6.02 for one monkey and 7.11 for another. All three BZs tended to increase average latency to respond. Apparent pKB and pA2 analysis may prove useful for elucidating receptor mechanisms involved in the behavioral effects of BZs. PMID:8748392

  10. Enhanced tonic inhibition influences the hypnotic and amnestic actions of the intravenous anesthetics etomidate and propofol

    PubMed Central

    Kretschmannova, Karla; Hines, Rochelle M.; Revilla-Sanchez, Raquel; Terunuma, Miho; Tretter, Verena; Jurd, Rachel; Kelz, Max B.; Moss, Stephen J.; Davies, Paul A.

    2013-01-01

    Intravenous anesthetics exert a component of their actions via potentiating inhibitory neurotransmission mediated by γ-aminobutyric type-A receptors (GABAARs). Phasic and tonic inhibition are mediated by distinct populations of GABAARs, with the majority of phasic inhibition by subtypes composed of α1-3βγ2 subunits, while tonic inhibition is dependent on subtypes assembled from α4-6βδ subunits. To explore the contribution that these distinct forms of inhibition play in mediating intravenous anesthesia we have used mice in which tyrosine residues 365/7 within the γ2 subunit are mutated to phenyalanines (Y365/7F). Here we demonstrate that this mutation leads to increased accumulation of the α4 subunit containing GABAARs in the thalamus and dentate gyrus of female Y365/7F but not male Y365/7F mice. Y365/7F mice exhibited a gender specific enhancement of tonic inhibition in the dentate gyrus that was more sensitive to modulation by the anesthetic etomidate, together with a deficit in long-term potentiation. Consistent with this, female Y365/7F, but not male Y365/7F mice exhibited a dramatic increase in the duration of etomidate and propofol mediated hypnosis. Moreover, the amnestic actions of etomidate were selectively potentiated in female Y365/7F mice. Collectively these observations suggest potentiation of tonic inhibition mediated by α4 subunit containing GABAARs contributes to the hypnotic and amnestic actions of the intravenous anesthetics, etomidate and propofol. PMID:23616535