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PubMed1989

[Clinical aspects of hypnotics].

Knowledge of benefits and risks of these substances are important for a low-risk-treatment with hypnotics. Different questions occur, such as short- oder long-acting hypnotics? Disturbing interactions? Duration of therapy? Risks of amnesia? Insomnia of old people? Alternatives to Benzodiazepin-Hypnotics? In each case the application of these hypnotics should follow along the "3 S Line": straight indication, small dose, short application. There does not exist an universal principle of therapy for people who suffer from insomnia. This serious disease is often very agonizing for them. As a pharmacologic instrument there is yet no alternative to Benzodiazepines.

Aged↗
PubMed1970

A comparative study of three hypnotics: methyprylon, glutethimide and chloral hydrate.

A controlled study designed to evaluate the hypnotic potentiality of methyprylon (300 mg.), glutethimide (500 mg.) and chloral hydrate (1000 mg.) was carried out on 50 in-patients experiencing long-standing insomina. The patients ranged in age from 21 to 60 years, the sexes were equally represented and the clinical diagnoses were psychoneurosis, reactive depression, or anxiety reaction. An interesting feature of the experimental design allowed for the exclusion of placebo reactors before the initiation of the main trials. No difference in effectiveness of maintaining sleep could be established among the three hypnotic agents, indicating that at the usual levels of statistical significance, all three agents were equally effective as hypnotics. However, a significant trend (P = .05) was found for methyprylon (Noludar) to be the most effective and chloral hydrate to be the least effective of the three drugs in maintaining sleep. Methyprylon was found statistically (P = .05) to be the fastest sleep-inducing agent, whereas glutethimide (Doriden) proved to be the slowest of the three hypnotics with respect to sleep induction time.

Adjustment Disorders↗
PubMed1977

A comparison of thalidomide and pentobarbital - new methods for identifying novel hypnotic drugs.

We have compared the sleep-producing effects of thalidomide and pentobarbital. In a dose range that did not produce ataxia, thalidomide increased slow wave sleep and rapid eye movement sleep in cats (2-8 mg/kg p.o.) and rats (16 mg/kg p.o.). Pentobarbital had hypnotic activity in the same dose range but produced ataxia also at these doses. Thalidomide reduced spontaneous activity of both mice and rats. This occurred over a dose range of 8 to 1000 mg/kg p.o., but plateaued at a level of activity well above the complete inactivity of anesthesia that occurred with pentobarbital at well above the complete inactivity of anesthesia that occurred with pentobarbital at doses (greater than or equal to 32 mg/kg p.o.) above the hypnotic range. Several simple screens for thalidomide-like activity have been described which, together, could facilitate the search for thalidomide-like hypnotics. Pentobarbital, at doses 3 to 10 times the hypnotic range, prevented audiogenic seizures in physically dependent rats withdrawn from sodium barbital but thalidomide did not substitute for barbiturates even at doses 30 times those that increased sleep. Thalidomide, but not pentobarbital, enhanced the sleep-producing effect of electrical stimulation of basal forebrain in cats. The latter two findings suggest that thalidomide probably has a mechanism of action different from that of pentobarbital and that this may involve the activation of a sleep center in the forebrain.

Animals↗
PubMed1995

[Insomnia and hypnotics].

This article outlines some of the new developments in the field of insomnia. To obtain a better understanding of insomnia and avoid the diversities of impractical diagnosis, the medical profession must universally agree on the classification of insomnia. This knowledge has to be available to all levels of the medical community, especially general practitioners. The article reviews some new data about classification, diagnosis, and treatment of insomnia. It discusses the definition of insomnia and sets up the accepted criteria for the severity of its various forms. The policy of using hypnotics in Norway is fairly restrictive. Only three hypnotics are available, two benzodiazepins (nitrazepam and flunitrazepam) and the newly introduced cyclopyrrolone (zopiclone). The mechanisms of action of various hypnotics on the gamma-aminobutyric acid system are briefly discussed, and guidelines are given for use and choice of hypnotics, their indications and contraindications. In any modern society like Norway, there should be a clear awareness of the impact of insomnia on the quality of life and the seriousness of the effects it can have on the everyday activities of subjects suffering from this disorder.

Humans↗
PubMed1995

[The comparison of hypnotic potency of nitrous oxide with that of sevoflurane: evaluation by the middle latency auditory evoked response].

In 10 consented patients (ASA I-II) we quantitated the hypnotic potencies of 0.7 MAC nitrous oxide and 0.7 MAC sevoflurane by measuring auditory evoked response (AER), and compared the hypnotic potency of nitrous oxide with that of sevoflurane at the same MAC. In each patient, measurements of AER waves were performed in the following three stages, 0.7 MAC nitrous oxide, 0.7 MAC sevoflurane and 0.7 MAC nitrous oxide after induction of anesthesia. Analysis of variance was used to compare the hypnotic potencies between two inhaled anesthetics. Pa and Nb latencies with sevoflurane were longer than those with nitrous oxide, and Pa and Nb amplitudes with sevoflurane were greater than those with nitrous oxide. However, we found that there were no statistical significances in our results. In conclusion, nitrous oxide exerts as much hypnotic effect as sevoflurane.

Analysis of Variance↗
PubMed1993

Hypnotics should never be used in patients with sleep apnea.

Although benzodiazepine medication is generally considered to be inappropriate for patients with obstructive sleep apnea, further investigation is required to evaluate this. Non-benzodiazepine hypnotics may improve sleep quality without causing respiratory depression. In central sleep apnea, hypnotics not only improve sleep but also decrease apnea frequency probably by reducing arousals and elevating arterial PCO2. Consequently, I submit that the statement 'hypnotics should not be used in patients with sleep apnea' should be changed to 'hypnotics may sometimes be used in patients with sleep apnea'.

Benzodiazepines↗
PubMed1995

Variation in prescribing of hypnotics, anxiolytics and antidepressants between 61 general practices.

BACKGROUND: Although the desirability of reducing prescribing of hypnotics and anxiolytics has long been recognized, variation between practices in patterns of psychotropic drug prescribing has received little attention; factors underlying such variation are poorly understood. AIM: The study aimed to describe the extent of variation between general practices in the prescribing of hypnotics, anxiolytics and antidepressants; it also aimed to analyse the influence of measures of practice population and general practice and general practitioner characteristics on any variation in prescribing volumes. METHOD: Routinely collected prescribing data and practice population data, from April 1992 to March 1993, from all 61 practices in the Cambridge and Huntingdon Health Commission were analysed. Prescribing was measured as annual defined daily doses per 1000 practice population for each drug class. Data on variables relating to practice structure and general practitioner characteristics were obtained and analysed. Potentially influencing variables were investigated by multiple regression. RESULTS: Between the highest and lowest prescribing practices there was an 11-fold difference, a 13-fold difference and an eightfold difference in the annual defined daily doses per 1000 practice population prescribed for hypnotics, for anxiolytics and for antidepressants, respectively. Strong positive correlations existed between volumes of prescribing of each drug class. The drugs prescribed in the greatest volumes were hypnotics. Practice population structure had some influence on psychotropic drug prescribing with high prescribing being associated with the proportions of temporary residents and women aged 65 years and over in the practice for all three classes of drug. Other factors, including presence of a practice counsellor, were not found to have a significant influence on psychotropic drug prescribing. CONCLUSION: The degree of variation in prescribing volumes of psychotropic drugs between practices raises serious concerns. Further study is needed, but progress will be hampered until there is more clarity over the effectiveness and appropriateness of using these substances in the various illness, symptom and life-stress presentations seen in primary care.

Adolescent↗
PubMed1997

Common quantitative trait loci for alcohol-related behaviors and central nervous system neurotensin measures: hypnotic and hypothermic effects.

Genetic correlations were found between high-affinity neurotensin receptor (NTR(H)) densities and NT-immunoreactivity (NT-ir) levels in specific brain regions and sensitivity to hypnotic and hypothermic effects of ethanol in LSXSS recombinant inbred strains of mice. Simple sequence length polymorphisms were used to identify quantitative trait loci (QTL) influencing hypnotic and hypothermic sensitivity to ethanol, NTR(H) and low-affinity neurotensin receptor densities and NT-ir levels in LSXSS recombinant inbred strains. Common QTL for NTR(H) receptor densities, NT-ir levels and these ethanol actions were identified. One of the QTL (chromosome 2, 80 cM) for NTR(H) density and hypnotic sensitivity is linked to the NTR(H) gene, Ntsr. Also, QTL for NTR(H) density were found in common with confirmed QTL for hypnotic sensitivity on chromosomes 1 (43 cM), 11 (57 cM) and 15 (56 cM) and with an unconfirmed QTL on chromosome 3 (19 cM). Two common QTL for NT-ir levels, but not NTR(H) or low-affinity neurotensin receptor receptors, and ethanol-induced hypothermia were observed on chromosomes 4 (43 cM) and 6 (41 cM). Two common QTL for NT-ir levels and sleep time were identified on chromosomes 3 (19 cM) and 9 (55 cM). Common QTL indicate that genes regulating NT receptor and/or NT-ir expression may be the same as those regulating sensitivity to ethanol.

Alcoholism↗
PubMed1997

Pharmacokinetic-pharmacodynamic characterization of the cardiovascular, hypnotic, EEG and ventilatory responses to dexmedetomidine in the rat.

This study characterizes the pharmacokinetic-pharmacodynamic (PK-PD) relationships of the cardiovascular, EEG, hypnotic and ventilatory effects of the alpha-2 adrenergic agonist dexmedetomidine in rats. Dexmedetomidine was administered by a single rapid infusion (n = 6) and by an infusion regimen of gradually increasing rate (n = 8). HR, mean arterial pressure (MAP) and EEG signals were recorded continuously, as was the time at which the rats woke up spontaneously from drug-induced sleep, a measure of hypnosis. Arterial concentrations of dexmedetomidine and blood gases were determined regularly. A sigmoidal Emax model was used to describe the HR, MAP and EEG concentration-effect relationships, with the EEG effect (activity in 0.5-3.5-Hz frequency band) linked to an effect-site model. The PK of dexmedetomidine could be described by a two-compartment model, with similar PK parameters for both infusion regimens. Plasma protein binding was 84.1[0.7]%. Because of complex cardiovascular homeostatic reflex mechanisms, HR and MAP could only be analyzed during gradually increasing infusions. The maximal decrease in HR was 35(2)%, and the maximal increase in MAP was 37(2)%. For both infusion regimens, similar PD parameters were found for the EEG and the hypnotic measure. These data suggest the absence of active metabolites or tolerance of the EEG and hypnotic effects. Judging on the basis of concentrations of dexmedetomidine (mean (S.E. M.)), HR decrease was the most sensitive response [EC50 of 0.65(0. 09) ng/ml], followed by increase in MAP [EC50 of 2.01(0.14) ng/ml], change in EEG activity [EC50 of 2.24(0.16) ng/ml] and the hypnotic measure [Cwake-up of 2.64(0.10) ng/ml]. Ventilatory effects were minor.

Adrenergic alpha-Agonists↗
PubMed1998

[Sleep disorders and the consumption of hypnotics on the island of Mallorca].

OBJECTIVE: To estimate the frequency and characteristic of sleep disorders and consumption of hypnotic drugs in a population attended by primary care physicians (PC). METHODS: Interviewing a population of 602 patients at the office exit of 87 PC physicians in 32 institution in Mallorca 1994. Questionnaire on sleep: hypnotic drugs and scale hospital anxiety-depression, others. RESULTS: 17.4% (95% CI: 14.4%-20.5%) sleepless (DSM-III-R), 27.0% (95% CI: 23.5%-30.6%) complained from poor sleep quality and 16.4% (95% CI: 13.4%-19.4%) usually consumed hypnotic drugs (56.7%, for longer than one year). CONCLUSION: The high frequency of both sleep disorders and chronic consumption of hypnotic drugs represents a relevant health problem.

Adolescent↗
PubMed1979

Methodology for demonstrating sustained efficacy of hypnotics: a comparative study of triazolam and flurazepam.

To test for sustained hypnotic efficacy, triazolam (0.6 mg) or flurazepam (30 mg) was given to chronic insomniac patients for 7 consecutive nights in parallel, double-blind design. Triazolam at this dose was an effective hypnotic by all usual subjective measures and did not produce appreciable hangover. Flurazepam performed similarly. For either drug, comparison of the mean scores for the first 2 nights with that for the last 2 nights for any of the parameters did not reveal any significant difference. Thus, both triazolam and flurazepam showed sustained efficacy for 1 week at these doses. Some interesting theoretical and practical questions about the measurement of sustained efficacy of hypnotics in situations of repetitive dosing were addressed by the study. While a placebo control is desirable, the results obtained may be uninterpretable. An acute-care hospital setting may not be the ideal setting for doing such studies. There were indications from the study that the first-night results in a hypnotic clinical trial may be atypical.

Adult↗
PubMed1991

Hypnotic efficacy of estazolam compared with flurazepam in outpatients with insomnia.

Estazolam is a new benzodiazepine hypnotic agent with an intermediate half-life of 12 to 15 hours. The authors designed an investigation to compare its hypnotic efficacy to that of flurazepam, generally considered the reference standard. The hypnotic efficacy of estazolam at two doses (1 mg and 2 mg) was compared with that of flurazepam (30 mg) in a double-blind, placebo-controlled, multicenter, 7-night study that involved 223 outpatients with insomnia. On subjective assessments of the patients, no differences were noted between estazolam 2 mg and flurazepam 30 mg on any of six sleep parameters. Patients who were receiving estazolam 1 mg rated their sleep significantly better than did patients who were receiving placebo on all parameters except sleep latency. Global evaluation of the physicians indicated significant improvement in quality of sleep, sleep depth, sleep duration, and nocturnal awakenings in all three active treatment groups; estazolam 2 mg and flurazepam also decreased sleep latency significantly. The percentage of patients who reported any adverse experience was 68% for flurazepam, 58% for estazolam 2 mg, and 54% for estazolam 1 mg; the incidence of adverse events in the placebo group was 43%. In conclusion, estazolam 2 mg was found to be as effective a hypnotic as flurazepam 30 mg. Estazolam 1 mg is also effective in the treatment of outpatients with insomnia, but to a lesser degree.

Adolescent↗
PubMed2004

Thirteen days: Joseph Delboeuf versus Pierre Janet on the nature of hypnotic suggestion.

The problem of post-hypnotic suggestion was introduced in 1884. Give a hypnotic subject the post-hypnotic command to return in 13 days. Awake, the subject remembers nothing yet nonetheless fulfills the command to return. How then does the subject count 13 days without knowing it? In 1886, Pierre Janet proposed the concept of dissociation as a solution, arguing that a second consciousness kept track of time outside of the subject's main consciousness. Joseph Delboeuf, in 1885, and Hippolyte Bernheim, in 1886, proposed an alternative solution, arguing that subjects occasionally drifted into a hypnotic state in which they were reminded of the suggestion. This article traces the development of these competing solutions and describes some of Delboeuf's final reflections on the problem of simulation and the nature of hypnosis.

Consciousness↗
PubMed1991

Enzyme inhibition by analgesic and hypnotic agents on anaerobic dehalogenation of halothane.

Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp(2)) and NADH-ferricyanide reductase (fp(1)) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656 microM and 2570 microM), chlorpromazine (49.7 microM and 68.1 microM), ketamine (24.9 microM and 64.4 microM), fentanyl (23.9 microM and 34.6 microM), hydroxyzine (19.2 microM and 50.8 microM), diazepam (17.0 microM and 13.9 microM), buprenorphine (11.2 microM and 22.4 microM), and pentazocine (1.96 microM and 6.67 microM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp(2) and fp(1) did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp(2) and fp(1) which are flavoproteins existing in the microsomal electron transport system.

Journal Article↗
PubMed1987

Hypnotic action of pentobarbital in mice: a possible mechanism.

The effect of GABA receptor agonists (THIP and baclofen) on the hypnotic activity (loss of righting reflex and sleep time) of pentobarbital in mice was investigated. Combinations of either THIP-pentobarbital or baclofen-pentobarbital interacted synergistically by increasing hypnotic activity. The GABAa receptor antagonist, bicuculline, decreased the hypnotic effect of THIP-pentobarbital combinations but not that of baclofen-pentobarbital combinations. These results suggest that the hypnotic activity of pentobarbital involves GABAa receptor function.

Animals↗
PubMed1996

Left hemisphere superiority for event-related potential effects of hypnotic obstruction.

Twenty-two highly hypnotizable subjects were run in a visual target detection task which compared hypnotic obstruction of the left and right visual fields over separate blocks. The visual event-related potentials (ERPs) to non-target stimuli revealed that hypnotic obstruction reduced the P200 component to stimuli in the right hemifield, but did not affect P200 for stimulation in the left hemifield. The earlier P100 and N100 were also reduced to hypnotic obstruction but not as preferentially for either hemifield, while the P300 was not significantly changed. Right visual field left hemisphere P200 reduction predicted suppression of behavioral response (button press) to hypnotically obstructed targets in both hemifields. The results are discussed in terms of Farah's model of a left hemisphere mechanism for image generation, and how highly hypnotizable subjects might use this mechanism to comply successfully with the suggestion of a hallucinated visually opaque barrier.

Adult↗
PubMed1989

Changes in electromyographically recorded human monosynaptic reflex in relation to hypnotic susceptibility and hypnosis.

The aim of the present experiment was to study how hypnotic susceptibility and hypnosis affect motoneuron excitability. In a first trial, human subjects were selected according to their hypnotic susceptibility. In a second trial, the Hoffmann (H) reflex amplitude of the soleus muscle was studied in 3 groups: (1) highly susceptible subjects during hypnosis with standardized suggestions of simple relaxation, anesthesia, analgesia and paralysis (group I), (2) highly susceptible subjects (group II), and (3) non-susceptible subjects (group III) during long-lasting control conditions. Surface Ag/AgCl electrodes were used to stimulate the posterior tibial nerve using a constant current stimulator and to record the soleus EMG. Analysis of variance was performed on the data. The linear correlation coefficient within groups was evaluated. The H reflex amplitude decreased significantly during the recording session in groups I and II and there was no change in group III. In group I the effect of different suggestions could not be distinguished from the effect of hypnotic relaxation. The decrements in H amplitude did not differ between groups I and II, suggesting that the effect was related to personality traits rather than hypnotic induction.

Electric Stimulation↗
PubMed1977

Evaluation of the efficacy and neural mechanism of a hypnotic analgesia procedure in experimental and clinical dental pain.

Previous research implicates an endogenous central pain inhibitory mechanism in opiate analgesia, analgesia produced by focal electrical stimulation of the brain, and acupuncture analgesia. This investigation evaluates the possibility that analgesia produced by hypnosis is also mediated by such a mechanism. Results suggest that hypnotic analgesia is unlikely to involve this central pain inhibitory mechanism since hypnotic analgesia is not altered by naloxone hydrochloride, a specific narcotic antagonist. Results further demonstrate that the hypnotic procedure used produces an unusually effective and reliable increase in pain threshold. This finding generalizes to the control of clinical dental pain, and suggests that hypnotic pain control is a more widespread phenomenon in the population than has been thought.

Adolescent↗