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PubMed1996

Nocturnal psychometric assessment of the hypnotic activity of low and normal doses of brotizolam.

The hypnotic activity of acute doses of 0.125 mg and 0.250 mg brotizolam (CAS 57801-81-7, Lendormin) was compared in a double-blind randomised placebo-controlled study. Forty-nine healthy female volunteers aged between 23 and 44 years were enrolled. Trial medication was administered sublingually at 9:15 p.m. and 9:30 p.m., respectively. The nocturnal investigations continued until 2:30 a.m. A final examination was performed in the morning after breakfast. Every 30 min mood was measured by visual analogue scales. A computerised psychometric test (CDT) over 8 min was undertaken in order to measure continuous attention under short-term memory load. The Digit Symbol Substitution Test (DSST) was performed every hour. The CDT was not evaluable due to significant baseline differences. A statistically significant sedative effect in the DSST was already found 30 min after administration of 0.250 mg brotizolam, while the effect of 0.125 mg brotizolam just failed to reach the threshold of significance. Both treatments showed equivalent efficacy at 0.5, 1.5 and 2.5 h after administration. After 3.5 and 4.5 h there was no statistically significant difference between placebo and 0.125 mg brotizolam. After 4.5 h 0.250 mg brotizolam still showed significant hypnotic activity compared to placebo and 0.125 mg brotizolam. No treatment effects on mood were apparent according to the visual analogue scales. Furthermore, no hangover effects were detected for any of the parameters measured. The pharmacodynamic results confirmed the duration of action of more than 4.5 of h 0.250 mg brotizolam found in earlier studies and suggest that 0.125 mg is as effective as 0.250 mg with regard to sleep onset disturbances but has a shorter duration of action.

Adult↗

PubMed1977

[Metabolism of hypnotic and sedative drugs in cholestasis (author's transl)].

Alterations of hepatic microsomal biotransformation in cholestasis were discussed. In experimental animals biotransformation of hypnotic and sedative drugs is impaired under cholestatic conditions in vivo. The endplasmic reticulum of the hepatocytes is hypertropic but is hypoactive with respect to drug metabolism, a condition which is partly due to interference to substances retained in cholestatic livers (bile salts) with drug biotransformation and to cytochrome P-450 diminution in the microsomal membranes. The activity of conjugating enzymes (phase II of biotransformation) remains unaffected. A similar situation exists in cholestatic patients in which drug elimination is altered. In vitro studies with human liver homogenate, microsomes, and liver slices confirm the animal experiments by showing that cytochrome P-450 as well as the metabolism of hypnotics are reduced in cholestasis.

Animals↗

PubMedDate not supplied

Effects of opioid antagonists on anticonvulsant and hypnotic activity of benzodiazepines.

The influence of naloxone and naltrexone on the hypnotic and protective efficacy of diazepam, chlordiazepoxide, clonazepam and estazolam against electroshock- and pentylenetetrazole-induced seizures was studied in mice. Naloxone and naltrexone significantly decreased the anticonvulsant effects of diazepam and estazolam, but they did not changed that of chlordiazepoxide and clonazepam in electroshock-induced tonic hindlimb extension. Protective effects of benzodiazepines against pentylenetetrazole-induced seizures were slightly diminished by naloxone and naltrexone (16 mg/kg). Opioid antagonists were able to reduce the duration of benzodiazepines-induced sleep at high dose (32 mg/kg) only. These findings suggest that the endogenous opioid system may participate in antiepileptic effects of benzodiazepines but not in their hypnotic activity.

Animals↗

PubMed1997

Hypnotic activities of N3-benzyl and xylyl substituted arabinofuranosyluracil.

N3-Substituted derivatives of arabinofuranosyluracil (1), methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyls (8, 9, 10) and alpha-phenethyl (11) derivatives, were synthesized and their CNS depressant effects were evaluated by intracerebroventricular (i.c.v.) injection in mice by using hypnotic activity and pentobarbital-induced sleep prolongation as indices. At a dose of 2.0 mumol/mouse, the values of mean sleeping time induced by 7, 8, 9, and 10 were 144, 154, 117, and 33 min, respectively. Although the alkyl (2-6) derivatives did not cause any hypnotic activity, some derivatives tested (5, 7-10) significantly prolonged the pentobarbital-induced sleeping time.

Animals↗

PubMed2002

Hypnotic suggestion and the modulation of Stroop interference.

BACKGROUND: Hypnosis has been used clinically for hundreds of years and is primarily a phenomenon involving attentive receptive concentration. Cognitive science has not fully exploited hypnosis and hypnotic suggestion as experimental tools. This study was designed to determine whether a hypnotic suggestion to hinder lexical processing could modulate the Stroop effect. METHODS: Behavioral Stroop data were collected from 16 highly suggestible and 16 less suggestible subjects; both naturally vigilant and under posthypnotic suggestion. Subjects were urged to only attend to the ink color and to impede reading the stimuli under posthypnotic suggestion. RESULTS: Whereas posthypnotic suggestion eliminated Stroop interference for highly suggestible subjects, less suggestible control subjects showed no significant reduction in the interference effect. CONCLUSIONS: This outcome challenges the dominant view that word recognition is obligatory for proficient readers, and may provide insight into top-down influences of suggestion on cognition.

Adult↗

PubMed1998

Hypnotic interviewing: the best way to interview eyewitnesses?

It has been suggested that hypnosis techniques may have the potential to enhance eyewitness memory in forensic investigations. However, laboratory research shows that increases in recall with hypnosis techniques are often associated with decreases in accuracy, false confidence in incorrect information, and increased suggestibility to leading questions and misleading post-event information. These problems limit the usefulness of hypnosis as an interviewing procedure. However, in practical investigations, many factors associated with hypnosis, apart from the hypnotic induction itself, might lead to memory enhancement compared with standard police interviews. For example, hypnotic interviewers, because of their psychological, clinical, and interpersonal skills, may be better interviewers than police officers. They may use effective interviewing strategies such as those associated with the "cognitive interview"; a procedure which has the potential to enhance recall by approximately 35% without the problems of memory distortion associated with hypnosis. It is concluded, therefore, that a cognitive interview procedure should be used in preference to hypnosis.

Bias↗

PubMed1977

Role-played and hypnotically induced simulation of psychopathology on the MMPI.

The differential effects of role-played vs. hypnotically induced simulation of a paranoid syndrome on diagnostic and validity scales of the MMPI were tested with 30 female undergraduate Ss. Hypnotized Ss given the paranoid syndrome suggestion simulated the MMPI more accurately than did role-playing Ss. The F scale and Gough F-K index of dissimulation identified the role-playing group, but not the hypnosis with simulation suggestion group. It was concluded that further refinement of the validity scales of the MMPI is needed to improve their effectiveness in detecting deception on this test.

Adolescent↗

PubMed1986

Predisposition for nightmares: a study of hypnotic ability, vividness of imagery, and absorption.

The relationships of nightmare frequency to hypnotic ability, vividness of visual imagery, and the tendency to become absorbed in fantasy-like experiences were examined. Subjects were 841 undergraduate university students who participated in group tests of hypnotic ability, after which they estimated the number of nightmares that they had experienced in the prior year. In addition, 406 of the subjects completed Marks' Vividness of Visual Imagery Questionnaire, and Rotenberg and Bowers' Absorption scale. Of the subjects, 76% reported experiencing at least one nightmare in the prior year; 8.3% indicated one or more per month. Individuals with frequent nightmares scored higher on hypnotizability, vividness of visual imagery, and absorption.

Attention↗

PubMed1988

The use of benzodiazepine hypnotics in the elderly.

An epidemiologic study was conducted to observe patient-reported use and effects of triazolam, flurazepam, and oxazepam taken at bedtime among 2260 outpatients age 65 years or older in Canada. The study used pharmacy-based enrollment, with participant follow-up through a 3-day diary and a telephone interview. The study also evaluated how the three benzodiazepine hypnotics were prescribed. Prescription information showed that 66% of the flurazepam prescriptions were for the highest strength, compared to 39% and 35% for triazolam and oxazepam, respectively. As patient age increased, the highest strength of each agent was prescribed less frequently. For all drugs, 53% of prescriptions were written for use as necessary (prn), and the proportion who received such prescriptions increased with age. Patient reports, however, revealed that 57% were using a hypnotic every day, and this regular use increased with advancing age. Regular daily use was more common among those who used triazolam and oxazepam (62%) than those who took flurazepam (42%).

Adolescent↗

PubMed1979

Midazolam compared with thiopentone as a hypnotic component in balanced anaesthesia: a randomized, double-blind study.

Midazolam is a short-acting water soluble benzodiazepine derivative. It is a hypnotic used for intravenous anaesthesia induction. The present investigation was designed in a prospective double-blind fashion to compare midazolam with thiopentone as hypnotic components in balanced anaesthesia. The study included 50 healthy patients undergoing relatively short surgical procedures. The results revealed that thiopentone is faster in onset than midazolam for induction of anaesthesia, with less variation of dose response. However, maintenance of anaesthesia was superior with midazolam, requiring fewer supplemental anaesthetic drugs, having better patient acceptance and providing more amnesia. Postoperative complications were very low with both techniques. Midazolam was surprisingly similar to thiopentone in most parameters including emergence time from anaesthesia. Midazolam is a new drug with potential both for induction of anaesthesia and maintenance of balanced anaesthesia.

Adult↗

PubMed2002

Usefulness of oral hypnotic premedication for volatile induction of anesthesia in adults.

PURPOSE: We investigated the effects of oral hypnotic premedication for smooth anesthetic induction and for the patient's comfort under anesthesia, using sevoflurane without nitrous oxide. METHODS: Adult patients were divided into four groups: control ( n= 12), triazolam (0.25 mg; n= 12), zopiclone (7.5 mg; n= 12), and clonidine (0.15 mg; n= 12) groups. Each premedication was given to each patient 1 h before the anesthesia. The patients breathed out to residual volume and then the anesthetic mask was fitted. The repeated vital capacity breathing technique was used, with 5% sevoflurane in 10 l.min(-1) oxygen. Induction time, specific induction side effects, and acceptability of this technique by the patients were recorded by an independent observer. RESULTS: Induction time in the premedicated groups ranged from 66 +/- 12 s (mean +/- SD) to 76 +/- 14 s, and these values were significantly shorter than that in the control group (92 +/- 16 s). The number of patients in whom adverse effects occurred during anesthetic induction was significantly greater in the control group (4 patients; 33%) than in the premedicated groups (1 patient each; 8%). Acceptability of the smell of sevoflurane was significantly higher in the premedicated groups (8-10 patients; 67%-83%) than in the control group (5 patients; 42%). CONCLUSION: Oral hypnotic premedications with either triazolam (0.25 mg), zopiclone (7.5 mg), or clonidine (0.15 mg) are recommended for smoother volatile anesthetic induction and for the patient's comfort in adults.

Journal Article↗

PubMed1990

Failure to limit quantities of benzodiazepine hypnotic drugs for outpatients: placing the elderly at risk.

PURPOSE: The long-term use of benzodiazepine hypnotics by the elderly is associated with serious side effects, and prescriptions of large quantities of these agents allow such use. Therefore, we determined the quantities of these agents prescribed to outpatients in our Veterans Administration teaching hospital, and the relationship of patient age to total number of doses prescribed per prescription. PATIENTS AND METHODS: Pharmacy and patient records related to 655 consecutive prescriptions for triazolam (Halcion) and flurazepam (Dalmane) were reviewed. Only 266 (41%) of the prescriptions were for 30 or fewer doses, while 178 (27%) were written for 180 or more doses. RESULTS: Thirty-six percent of prescriptions for patients aged 65 years or older were for 180 or more doses, compared with 24% for those aged 45 to 64 years old, and 16% of the prescriptions for patients less than 45 years old (p less than 0.0001). In a multivariate analysis controlling for six other factors related to the total number of doses prescribed, patients aged 65 years or older were still more likely to receive a prescription for 180 or more doses (relative risk 1.9, 95% confidence interval 1.3, 2.8). CONCLUSION: We conclude that inappropriately large quantities of benzodiazepine hypnotics were commonly prescribed, and that patients aged 65 years or older were at greatest risk for receiving such prescriptions.

Age Factors↗

PubMed1990

Hypnotics and behavior.

Evaluation of the effects of hypnotics on waking behavior has primarily focused on two issues: (1) how these drugs affect performance the day after a nightly dose; and (2) how they affect memory processes, with special emphasis on anterograde amnesia. In terms of the relations between pharmacologic properties and residual effects, three conclusions can be drawn. First, dose is a major determinant of the presence or absence of morning effects. Every drug studied to date, if given in high enough dose, has produced morning performance decrements. Second, the longer-acting a compound, the more likely it is that a performance decrement will be observed. Finally, some data suggest that behavioral tolerance to the residual effects of hypnotics develops. The observation that benzodiazepines produce amnesia emerged from reports of their clinical use as presurgery medications. Although the initial reports involved intravenous diazepam and were anecdotal in nature, subsequent studies have demonstrated that amnesia is a characteristic of all the benzodiazepines, with the magnitude of the effect being a function of route of administration, dose, and the pharmacokinetics of the particular drug.

Anti-Anxiety Agents↗

PubMed1982

An assessment of the state hypothesis of animal "hypnosis' through an analysis of neocortical and hippocampal EEG in spontaneously immobile and hypnotized rabbits.

Hippocampal and neocortical EEG was studied in spontaneously immobile rabbits and in immobilized rabbits, "animal hypnosis.' Neocortical low voltage fast activity (LVFA) and hippocampal rhythmical slow activity (RSA) occurred spontaneously and were elicited by sensory stimulation, eserine and brain stimulation in normally immobile and hypnotized animals. Atropine sulfate blocked the LVFA and RSA that occurred during spontaneous immobility and hypnosis but not the LVFA and RSA that occurred during movement. RSA was also recorded from both CAI and dentate gyrus generators of the hippocampus during both types of immobility. The results show that hypnotized rabbits have the same type II (atropine-sensitive) EEG that is found in spontaneously immobile rabbits. The presence of type II EEG during hypnosis and its sustained sensitivity to stimulation is compatible with the view that the EEG activity is not uncoupled from its normal behavioral correlates. Perhaps normal EEG during animal hypnosis allows normal sensorimotor functions. This may permit the possibility of escape from predators at opportune moments once the immobility has served its defensive function.

Animals↗

PubMed1984

Hypnotic action of ethyl beta-carboline-3-carboxylate, a benzodiazepine receptor antagonist, in cats.

The present study demonstrates that ethyl beta-carboline-3-carboxylate (beta-CCE), a benzodiazepine receptor antagonist, has hypnotic and sedative actions in cats. Moreover, at a dose that does not by itself affect sleep, beta-CCE reverses the action of diazepam on sleep organization. The hypnotic effect of subcutaneous administration of beta-CCE (5 mg/kg) lasts for 3-4 h. During this period, deep slow wave sleep (deep non-REM sleep) and paradoxical sleep (REM sleep) significantly increase, while wakefulness markedly decreases. These results, which are quite opposite to the effects of benzodiazepines on sleep organization in cats, support the notion that beta-CCE also acts as a benzodiazepine antagonist of sleep organization.

Animals↗

PubMed1988

Hypnotic action of flunitrazepam in the rat: does 5-HT mechanism play a role?

This study examined whether pharmacological manipulation of serotonergic (5-HT) systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or combined with parachlorophenylalanine (pCPA), an inhibitor of the synthesis of 5-HT, 8-OH-DPAT, a 5-HT1A receptor agonist and fluvoxamine, an inhibitor of the reuptake of 5-HT. Flunitrazepam increased the amount of orthodox sleep, the latency of rapid eye movement (REM) sleep and decreased the amount of REM sleep. The drug pCPA decreased the total sleep time and the amount of orthodox and REM sleep. Administration of flunitrazepam to pCPA-pretreated rats induced orthodox sleep in an identical way to that found in the controls. The drug 8-OH-DPAT increased wakefulness and the latency of REM sleep. The association of flunitrazepam with 8-OH-DPAT abolished the increase in waking seen after 8-OH-DPAT alone. In contrast, the combined treatment with flunitrazepam and 8-OH-DPAT resulted in a lengthening of the latency of REM sleep significantly greater than that observed with the same dose of each drug alone. Fluvoxamine increased the latency a decrease the amount of REM sleep. The association of fluvoxamine with flunitrazepam induced a decrease in REM sleep, equal to the sum of the effects of the two drugs alone. Fluvoxamine did not modify the other effects of flunitrazepam. The present experiments demonstrate that the association of pCPA, 8-OH-DPAT and fluvoxamine, did not alter the hypnogenic effect of flunitrazepam. The possibility of an involvement of 5-HT mechanisms in the effect of flunitrazepam on the phasic events in sleep is questionable.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1986

Sedative-hypnotic anomalies related to dose of pentobarbital in long-sleep and short-sleep selectively-bred mice.

Hypnotic effects following administration of three doses of pentobarbital were evaluated in mice selectively-bred for differential hypnotic sensitivity to ethanol. Although the ethanol-sensitive Long-Sleep (LS) line displays greater sedation to a wide variety of CNS depressants (alcohols, barbiturates, benzodiazepines, general anesthetics), when compared to the ethanol-insensitive Short-Sleep (SS) line, the response pattern to pentobarbital remains equivocal. Thus, to clarify the effect of pentobarbital, certain variables (dose, sex, circadian rhythmicity) believed to be important in the expression of sleep time were evaluated. For all doses examined "sex" and "time of day tested" impacted on sleep time. With these provisos, 40 mg/kg consistently induced shorter sleep time in SS mice. The 60 mg/kg dose either failed to distinguish these two lines, or induced greater sleep times in the SS mice. The 80 mg/kg dose tended to have the same effect as the 60 mg/kg dose, but to a greater degree. Overall, it appears that for each line the dose response curve for pentobarbital is sigmoidal, but that the slope of the curve for the middle range of doses is greater for the SS line. Since pentobarbital has a unique effect on these lines of mice that is dissimilar to those reported for other barbiturates, the implication is that an additional factor, that is unimportant for other barbiturates, is essential for pentobarbital-induced hypnosis. Factors that could be responsible for this effect include differential metabolism of Gabaergic receptor dynamics.

Animals↗

PubMed1988

A psychophysiological differentiation between hypnotic behaviour and simulation.

Psychophysiological differentiation between conditions of hypnosis and simulation were examined with markers evolved from a series of experiments charting neuropsychophysiological accompaniments of hypnotic behaviour. Eighteen subjects participated in two sessions in which bilateral electrodermal activity was monitored to moderate intensity tones. Measurement in Session I, a Baseline-Control, of individual variation in rates of habituation of orienting responses, non-specific responses and tonic levels of skin conductance, enabled allocation of matched groups to Session II in which the same auditory stimuli were mixed with a taped hypnotic induction. Half the subjects were instructed to fake hypnosis and the others to comply. In session II the groups were differentiated as follows: (1) rate of habituation to the tones was retarded in the simulation condition and facilitated in the hypnosis condition compared with baseline; (2) the incidence of non-specific electrodermal responses was elevated in simulators after instructions to 'fake hypnosis'; (3) right-hand levels of skin conductance were elevated in simulators; (4) all but one subject in the hypnosis condition admitted to hearing the tones whereas all but one in the simulation condition claimed not to have heard them.

Adolescent↗