Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HYPNOTICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1993

Hypnotics as concurrent medication in depression. A placebo-controlled, double-blind comparison of flunitrazepam and lormetazepam in patients with major depression, treated with a (tri)cyclic antidepressant.

The addition of benzodiazepine hypnotics to a treatment with tricyclic antidepressants has received little systematic study. In a double-blind placebo-controlled design, the effects on mood and on sleep of two benzodiazepine hypnotics (lormetazepam and flunitrazepam) were studied in patients with major depression who were also treated with maprotiline or nortriptyline. After 4 weeks of combined treatment, lormetazepam resulted in a significantly greater decrease in the score on the Hamilton Depression Subscale than placebo, while there was a non-significant trend in favour of lormetazepam in comparison with flunitrazepam. With respect to sleep EEGs, lormetazepam resulted in a significantly greater suppression of REM sleep. The differences between lormetazepam and flunitrazepam may be partly explained by the shorter half-live of lormetazepam.

Adult↗
PubMed1994

Effects of zopiclone on sleep and symptoms in schizophrenia: comparison with benzodiazepine hypnotics.

Sleep variables and psychiatric symptoms were investigated in 6 male chronic schizophrenic outpatients. The patients were being treated with benzodiazepine (BZD) hypnotics for more than 8 weeks, and BZDs were replaced with zopiclone (ZPC) 15 mg/day. Polysomnographic examinations, subjective sleep assessments and BPRS scoring were performed during BZD therapy and at the end of 8 weeks of ZPC therapy. The doses of neuroleptics and anticholinergic agents remained fixed throughout the study. The amount of slow-wave sleep (SWS) was markedly small and that of stage 1 sleep was moderately large during BZD therapy. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. There were no significant change in the amount of SWS between the treatment. Half of the patients exhibited a sleep-onset REM period (SOREMP) during ZPC therapy. Both total BPRS score and negative symptom score were lower during treatment with ZPC than BZDs. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZD hypnotics and that reduced SWS and SOREMP may be partly involved in the pathophysiology of schizophrenia.

Adult↗
PubMed1996

Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of antagonism by flumazenil.

In this double-blind, placebo-controlled study we investigated whether 10 mg flumazenil, a pure benzodiazepine antagonist, can block the hypnotic and hypothermic effects of 3 mg melatonin. The design comprised four 7-h (1200-1900 h) testing periods, preceded by a 'no-treatment' adaptation period of the "7/13' sleep-wake paradigm. Six young healthy adult males were paid to participate. During each experimental period, tablets were administered at 1145 h (flumazenil or placebo) and at 1200 h (melatonin or placebo) in a randomized, double-blind, partially repeated Latin square design. Polysomnographic recordings and core body temperature recordings revealed that melatonin, either in combination with placebo or with flumazenil, significantly increased the amounts of sleep, and decreased core body temperature in comparison with placebo alone or the combination of flumazenil plus placebo. These results do not support the hypothesis that melatonin exerts its hypothermic and hypnotic effects via the central benzodiazepine receptors.

Adult↗
PubMed1981

Use of gastric fistula rats for the study of sedative, hypnotic and antianxiety drugs.

A rat gastric fistula preparation has been developed for the ready and safe administration of water-insoluble drugs. Graded doses of five sedative hypnotics - pentobarbital, secobarbital, methaqualone, diazepam and chloral hydrate - were studied using this preparation and a behavioral scale. The effect of these drugs on respiratory rate was also studied. The rat gastric fistula preparation is a stable one which allows the execution of crossover studies lasting for several months. Valid assays were obtained in comparisons of pentobarbital, secobarbital and methaqualone using both total behavior scale scores (BSS) and depression of respiratory rate. Secobarbital was equipotent to and methaqualone one-fourth as potent as pentobarbital. The slope of the chloral hydrate BSS dose-response line was statistically significantly steeper than that of pentobarbital. The diazepam BSS dose-response line was not only significantly less steep than that of pentobarbital but a plateau was seen. Neither chloral hydrate nor diazepam produced a dose-related depression of respiratory rate. The rat gastric fistula preparation has thus proved useful in characterizing the pharmacologic profiles, dose-response relationship and relative potencies of sedative hypnotics.

Animals↗
PubMed1986

Pharmacology of lemongrass (Cymbopogon citratus Stapf). III. Assessment of eventual toxic, hypnotic and anxiolytic effects on humans.

A herbal tea (called an abafado in Brazil) prepared from the dried leaves of lemongrass was administered to healthy volunteers. Following a single dose or 2 weeks of daily oral administration, the abafado produced no changes in serum glucose, urea, creatinine, cholesterol, triglycerides, lipids, total bilirubin, indirect bilirubin, GOT, GPT, alkaline phosphatase, total protein, albumin, LDH and CPK. Urine analysis (proteins, glucose, ketones, bilirubins, occult blood and urobilinogen) as well as EEG and EKG showed no abnormalities. There were slight elevations of direct bilirubin and of amylase in some of the volunteers, but without any clinical manifestation. These results taken together indicate that lemongrass as used in Brazilian folk medicine is not toxic for humans. The eventual hypnotic effect of lemongrass was investigated in 50 volunteers who ingested samples of lemongrass and a placebo under double-blind conditions. The parameters (i.e. sleep induction, sleep quality, dream recall and rewakening) did not show any effect of lemongrass as compared to the placebo. Eighteen subjects with high scores of trait-anxiety were submitted to an anxiety-inducing test following taking lemongrass or placebo under double-blind conditions. Their anxiety levels were similar, indicating that the abafado of the plant does not have anxiolytic properties. It is concluded that lemongrass, one of the most popular Brazilian herbal medicines, used for its alleged CNS-depressant effects, is atoxic but lacks hypnotic or anxiolytic properties.

Administration, Oral↗
PubMed1993

The use of tranquilizers, hypnotics and analgesics among 18,592 Finnish adults: associations with recent interpersonal conflicts at work or with a spouse.

The use of tranquilizers, hypnotics, and analgesics was assessed by a postal questionnaire in a nationwide sample of 18,592 adults aged from 24 to 65 years: 14,800 employees, 2105 housewives and 687 unemployed persons. The use of tranquilizers was most frequent among unemployed persons whereas housewives did not use the studied medicines more than the employed women. In the multivariate analyses (adjusted for age, social class and neuroticism) unmarried status was associated with the use of tranquilizers and hypnotics among both genders. Reported recent interpersonal conflicts both at work and with a spouse were associated with the use of tranquilizers among men, whereas among women significant associations were found only for conflicts with a spouse. These results indicate that domestic factors are more likely to predict women's tranquilizer use.

Adult↗
PubMed2004

[Clinical applications of intravenous anaesthetics pharmacology: the example of hypnotics and opioids].

OBJECTIVE: To review the general principles of pharmacokinetics and pharmacodynamics models by focusing on intravenous anaesthetics (hypnotics and opioids). DATA SOURCES: Medline references, lectures from the French congress of anaesthesiology and intensive care medicine, abstracts. DATA SYNTHESIS: Pharmacokinetic and pharmacodynamic modelling allows simple estimation of becoming of anaesthetic drugs in the body, instead of classical pharmacologic approach. However, pharmacokinetic as well as pharmacodynamic parameters are often considered as resulting from complex mathematic approaches and remain then poorly used in practice by physicians. The aim of this article is to simply expose concepts underlying PK-PD models building and to explain significance of the main PK-PD parameters (first-order rate constants, k(e0), T(1/2)k(e0), T(peak), context-sensitive half-time, context-sensitive decrement times). Clinical consequences for using intravenous anaesthetic drugs (hypnotics and opioids) are exposed either during bolus injection or continuous infusion, when injected alone or co-administered.

Anesthesia, Intravenous↗
PubMed2006

Intracerebroventricular injection of L-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks.

Four experiments were conducted to clarify the central functions of L-serine and its analogs on an acute stressful condition. Intracerebroventricular (i.c.v.) injection of L-serine (0.21, 0.42 and 0.84 micromol) attenuated stress responses in a dose-dependent fashion, as well as induced sleep, in Experiment 1. The effects of L- and D-serine in Experiment 2, those of L-serine, phosphoserine, acetylserine and L-cysteine in Experiment 3 and those of L-serine, glycine and lysophosphatidylserine in Experiment 4 were compared at an equimolar basis (0.84 micromol). D-Serine, proposed as an endogenous agonist of N-methyl-D-aspatate (NMDA) receptor, did not have sedative and hypnotic effects as observed with L-serine. In contrast, all the analogs and derivatives of L-serine had a sedative effect, although with a different manner in several behavioral markers of stress such as spontaneous activity and distress vocalizations. No significant changes in plasma corticosterone concentration were observed in any experiment. Taken together, the i.c.v. injection of L-serine analogs and its derivatives have sedative and hypnotic effects under an acute stressful condition, which does not involve the hypothalamic-pituitary-adrenal axis. In conclusion, L-serine may be effective in improving anxiety or sleep disorders induced by psychological stressor.

Age Factors↗
PubMed2004

Tetrandrine, a bisbenzylisoquinoline alkaloid from Chinese herb Radix, augmented the hypnotic effect of pentobarbital through serotonergic system.

This is the first study of hypnotic activity of tetrandrine (a major component of Stephania tetrandrae) in mice by using synergism with pentobarbital as an index for the hypnotic effect. The results showed that tetrandrine potentiated pentobarbital (45 mg/kg, i.p.)-induced hypnosis significantly by reducing sleep latency and increasing sleeping time in a dose-dependent manner, and this effect was potentiated by 5-hydroxytryptophan (5-HTP). In the subhypnotic dosage of pentobarbital (28 mg/kg, i.p.)-treated mice, tetrandrine (60 and 30 mg/kg, p.o.) significantly increased the rate of sleep onset and also showed synergic effect with 5-HTP. Pretreatment of p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping time and tetrandrine abolished this effect. From these results, it should be presumed that serotonergic system may be involved in the augmentative effect of tetrandrine on pentobarbital-induced sleep.

Alkaloids↗
PubMed2005

Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid by LC-MS/MS.

A procedure is presented for the screening of 17 benzodiazepines and hypnotics in oral fluid after collection with the Intercept(R) device by LC-MS/MS (alprazolam, 7-aminoclonazepam, 7-aminoflunitrazepam, bromazepam, clobazam, diazepam, lorazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam, tetrazepam, triazolam, zaleplon, zopiclone and zolpidem). The method involves extraction of 0.5 mL of oral fluid (previously stored in the Intercept blue buffer) treated with 0.5 mL of phosphate buffer (pH 8.4) in the presence of 5 ng diazepam-d(5) used as internal standard, with 3 mL of diethyl ether/methylene chloride (50/50) and separation using liquid chromatography-tandem mass spectrometry. The limits of quantification for all benzodiazepines and hypnotics range from 0.1 to 0.2 ng/mL. Linearity is observed from the limit of quantification of each compound to 20 ng/mL (r(2)>0.99). Coefficients of variation at 2 ng/mL, measured on 6 points range from 4 to 8% for all drugs, except zopiclone (34%). Extraction recovery, measured at the same concentration was higher than 90%. Ion suppression was evaluated for each compound and was lower than 10% for all drugs except zopiclone (93%). These results were found suitable to screen for 17 benzodiazepines in oral fluid and detect them at very low concentrations, making this method suitable for monitoring subjects under the influence.

Benzodiazepines↗
PubMed2005

Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry.

A procedure is presented for the screening of 16 benzodiazepines and hypnotics in human hair by LC-MS/MS (alprazolam, 7-aminoclonazepam, 7-aminoflunitrazepam, bromazepam, clobazam, diazepam, lorazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam, tetrazepam, triazolam, zaleplon and zolpidem). The method involves decontamination of hair with methylene chloride, hair cut into small pieces, incubation of 20 mg in phosphate buffer (pH 8.4) in the presence of 1 ng diazepam-d5 used as internal standard, liquid-liquid extraction with diethyl ether/methylene chloride (10/90) and separation using liquid chromatography-tandem mass spectrometry. The limits of quantification for all benzodiazepines and hypnotics range from 0.5 to 5 pg/mg using a 20-mg hair sample. Linearity is observed from the limit of quantification of each compound to 200 pg/mg (r2 > 0.99). Coefficients of variation measured on six points and at two concentrations (10 and 50 pg/mg) range from 5 to 20% for all drugs but one. Extraction recovery, measured at the two same concentrations range from 32 to 76%. These results were found suitable to screen for 16 benzodiazepines in hair and detect them at very low concentrations, making this method suitable to monitor single dose.

Benzodiazepines↗
PubMed2006

Sedative and hypnotic activities of the ethanol fraction from Fructus Schisandrae in mice and rats.

Fruits of Fructus Schisandrae have been used as medicine for the treatment for insomnia in traditional Chinese medicine. In the present research, the sedative and hypnotic activities of the ethanol fraction of Fructus Schisandrae fruit (SY3) were studied in mice and rats. In the open field test, SY3 (25, 50 and 100 mg/kg) significantly inhibited the motor activity of mice compared to the normal. Results also showed SY3 potentiated pentobarbital-induced sleep by not only increasing the number of falling asleep and prolonging sleeping time but also reducing sleep latency. Furthermore, sleep-wake stages of rats were evaluated by polytrophic recording for 3 h after treatment. The results demonstrated that SY3 at doses of 20, 40 and 80 mg/kg behaved remarkable action on sleep architecture of rats, which contain the increase of total sleeping time, the rate of deep slow wave sleep (SWS) and mean episode duration of deep SWS, and the decrease of the latency of deep SWS. Therefore, these results suggest that the ethanol fraction of Fructus Schisandrae fruit possesses potent sedative and hypnotic activity, which supported its therapeutic use for insomnia.

Animals↗
PubMed2006

Gene expression in the rat cerebral cortex: comparison of recovery sleep and hypnotic-induced sleep.

Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABA(B) ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the omega1 site on the GABA(A) receptor/Cl(-) ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.

Analysis of Variance↗
PubMed2005

Acute neurophysiological effects of the hypnotic zolpidem in healthy volunteers.

INTRODUCTION: The imidazopyridine zolpidem is a hypnotic drug with relative selectivity for the benzodiazepine (BZP) type 1 receptor subtypes displaying a different biochemical structure to that of BZPs. Little is known of its electrophysiological effects. PURPOSE: The aim of the present study was to investigate the acute neurophysiological effects of clinical oral doses of zolpidem. METHODS: This was a double blind, independent group design study. Thirty-six young, healthy volunteers were randomly allocated to one of three groups--zolpidem (5 mg and 10 mg) and placebo. In addition to ERPs, behavioural measures were used to examine sedative effects of the drug. RESULTS: ERPs were affected in a similar way to that described after sedative/hypnotic drug ingestion: increased N2 and P3 latencies and decreased N2 and P3 amplitudes. However, contrary to what is expected of a hypnotic drug, there was no change with N1 while P2 amplitude increased after the highest dose. CONCLUSIONS: Because zolpidem showed different effects in different components, it seems to first enhance or preserve initial orienting (no change in N1), after an increase of P2 and then drastically diminish resource allocation (affecting N2 and P3 latencies and amplitudes). The study with ERPs, therefore, allows a more direct "moment to moment" investigation of finer mechanisms of changes in cerebral processes underlying the acute ingestion of the drug in question. The effects on N2 and P3 amplitudes and latencies were similar to those of other sedative/hypnotic drugs. However, zolpidem led to an unexpected increase in P2 amplitude; this effect may be related to its selective receptor binding profile and warrants further research.

Adult↗
PubMed2005

Long-term use of sedative hypnotics in older patients with insomnia.

BACKGROUND AND PURPOSE: Insomnia is a common problem that increases with age and can last months to years. While substantial data establish the efficacy and safety of short-acting hypnotic therapy for the management of short-term insomnia using benzodiazepines receptor agonists (BzRAs), there are few studies on the continued efficacy and safety of these drugs when used for sustained periods. This paper reports the results of a 1-year open-label extension phases of two randomized, double-blind trials of zaleplon. PATIENTS AND METHODS: In the open-label phase, older patients self-administered zaleplon nightly from 6 to 12 months and were then followed through a 7-day single-blind placebo-controlled run-out period. RESULTS: The safety profile in this population of older adults was similar to that observed in a short-term trial of an equivalent population. The data also suggested that long-term therapy produced and maintained statistically significant improvement in time to persistent sleep onset, duration of sleep and number of nocturnal awakenings (P<0.001 for each variable) for treatment durations of up to 12 months. Discontinuation was not associated with rebound insomnia. CONCLUSION: The open-label trial of long-term hypnotic therapy with zaleplon 5 and 10 mg suggests that they are safe and effective for the treatment of insomnia in older patients. Placebo-controlled, double-blind trials are needed in zaleplon and other BzRAs to confirm these results.

Acetamides↗
PubMed1997

Flumazenil reverses the decrease in the hypnotic activity of pentobarbital by social isolation stress: are endogenous benzodiazepine receptor ligands involved?

Long-term social isolation stress has been shown to cause a decrease in pentobarbital (PB)-induced sleeping time in mice. In the present study, to clarify whether the GABAA/benzodiazepine (BZD) receptor system is involved in the decrease in the hypnotic activity of PB by social isolation stress, we examined the effects of BZD receptor ligands on the PB-induced sleep in group-housed and socially isolated mice. Moreover, we also tested whether social isolation stress affects the ability of GABA to stimulate 36Cl- uptake or the modulatory effect of diazepam and PB and GABA-induced stimulation of 36Cl- uptake into synaptoneurosomes prepared from mouse brain. Social isolation stress significantly decreased the PB-induced sleeping time in mice. The BZD receptor diazepam (0.1-0.8 mg/kg, i.p.) dose-dependently prolonged PB sleep in group-housed and isolated mice, but the effect was weaker in isolated mice. In contrast, FG7142 (5-10 mg/kg, i.p.), a BZD receptor inverse agonist, shortened the sleep in group-housed but not in isolated mice. Flumazenil (16.5-33 nmol, i.c.v.), a selective BZD receptor antagonist, caused PB sleep in isolated mice to return to the level of group-housed mice, at the dose that antagonized the effects of diazepam and FG7142 on PB sleep in group-housed mice. However, this antagonist alone produced no effect on PB sleep in group-housed mice. Social isolation stress decreased the ability of GABA (0.6-200 microM) to stimulate 36Cl- uptake into synaptoneurosomes but this stress had no effect on PB- and diazepam-induced enhancement of GABA-stimulated 36Cl- uptake. These results suggest that endogenous substance(s) with an inverse BZD receptor agonist-like property and the changes in the ability of GABA to stimulate chloride ion channels are involved in the decrease in the hypnotic activity of pentobarbital following social isolation stress.

Animals↗
PubMed2003

The GABA(A) receptor mediates the hypnotic activity of melatonin in rats.

The present investigation assessed whether hypnotic activity of melatonin was mediated by the GABA(A) receptor in rats. Electroencephalography (EEG) was measured in this experiment. Melatonin, at a dose of 10 mg/kg ip, showed a significant sleep-promoting effect in rats. Flumazenil (3.5 and 7 mg/kg), a specific antagonist of the benzodiazepine (BZP) recognition site on the GABA(A) receptor, and picrotoxin (2 and 4 mg/kg), the ligand of the picrotoxin site on the GABA(A) receptor, seemed to be devoid of intrinsic influence on each sleep parameter when used alone, but they significantly antagonized the melatonin-induced increase in total sleep time (TS), slow-wave sleep time (SWS) and paradoxical sleep time (PS), and the decrease in time to sleep onset (TSO) and wakefulness time (W). A significant interaction was shown between melatonin and flumazenil or picrotoxin. When bicuculline methiodide (2 and 4 mg/kg), a specific antagonist of the GABA binding site on the GABA(A) receptor, was used together with melatonin, the melatonin-induced increase in TS, SWS and PS, and the decrease in W were abolished. However, there was no interaction between melatonin and bicuculline methiodide on sleep parameters except PS. These results indicate that the hypnotic activity of melatonin may be linked to the GABA(A) receptor and mediated through the BZP recognition site, the picrotoxin site on the GABA(A) receptor and partially through the GABA binding site on the GABA(A) receptor.

Animals↗
PubMed2003

Antinociceptive and hypnotic effects of Premna tomentosa L. (Verbenaceae) in experimental animals.

Medicinal plants are believed to be an important source of new chemical substances with potential therapeutic effects. The research into plants with alleged folklore use as pain relievers should therefore be viewed as a fruitful and logical research strategy in the search of new analgesic drugs. In the present inquiry, antinociceptive effects of Premna tomentosa (PT) leaf extract (in methanol) were explored in experimental animals by acetic acid-induced writhing, tail flick and tail clip tests. Oral administration of PT extract at different doses (100, 200, 400 and 500 mg/kg) led to significant antinociceptive effects. The extract was also tested for hypnotic effects. Treatment with extracts at different doses (100, 200, 400 and 500 mg/kg) decreased the locomotor activity and potentiated the pentobarbitone-induced sleep time. The responses were dose-dependent. On the basis of the present finding, we can conclude that PT possesses antinociceptive and hypnotic activities.

Acetic Acid↗