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Hypnotic susceptibility and dream characteristics.

This study examined the relationship of hypnotic susceptibility to a variety of dream characteristics and types of dream content. A Dream Questionnaire was constructed synthesizing Gibson's dream inventory and Hilgard's theoretical conceptions of hypnosis. Employing the Harvard Group Scale of Hypnotic Susceptibility and the Field Inventory for evaluating hypnotic response, several dream dimensions correlated significantly with hypnotizability. For subjects as a whole, the strongest correlates were the frequency of dreams which they believed to be precognitive and out-of-body dreams. Ability to dream on a chosen topic also correlated significantly with hypnotic susceptibility for both genders. For females only, there was a negative correlation of hypnotic susceptibility to flying dreams. Absorption correlated positively with dream recall, ability to dream on a chosen topic, reports of conflict resolution in dreams, creative ideas occurring in dreams, amount of color in dreams, pleasantness of dreams, bizarreness of dreams, flying dreams and precognitive dreams.

Adolescent↗

Hypnotic drugs for 1984.

It is still insufficiently recognised that hypnotics and anti-anxiety drugs are one and the same and that the regular intake of these drugs will be followed by withdrawal phenomena, including complaints of insomnia and anxiety. The long-acting, cumulative drugs like phenobarbitone or flurazepam cannot in reality be withdrawn abruptly owing to their persistence in the tissues, and so they do not cause sharp rebound phenomena, though they cause impaired skills and judgement by day. Very short life drugs, like triazolam, are followed by immediate and severe withdrawal insomnia in older people and their regular nighttime intake may cause regular daytime withdrawal symptoms of enhanced anxiety. A hypnotic with a half-life of about 10 hours may be the most sensible compromise to provide sleep by night without serious positive or negative daytime effects, though some eventual withdrawal features will be inevitable. The benzodiazepines lead to a degree of tolerance, but this is never complete and their positive effects are sustained over many months. Increased sleep duration has been assumed to be a necessary feature of an effective hypnotic. However, hypnotic drugs for the future might not lengthen sleep, but improve it's restorative value and the subjective satisfaction given to the patient.

Adult↗

Residual effects of hypnotic drugs: evidence for individual differences on vigilance.

Twelve healthy volunteers were given butobarbitone 100 and 200 mg, nitrazepam 5 and 10 mg and 2 lactose dummy treatments, at 23.00 hours at weekly intervals over 6 weeks according to a balanced design and using double blind conditions. Performance was studied between 09.00 hours and 17.00 hours the following day. Significant (P is less than 0.05) impairment of tapping rate and digit symbol substitution occurred. No significant differences occurred between performance after active drug and dummy in auditory vigilance, and subjective effects. Examination of individual differences in the response of subjects to the 4 hypnotic drug treatments, compared with their responses after dummy, indicated that subjects could be divided into two groups. One group consistently rated themselved as more alert after hypnotics and their vigilance performance improved. The other group consistently were more drowsy after hypnotics and their performance was impaired. It is suggested that the improvement in the first group resulted from improved sleep quality sufficient to counteract the residual effect of the hypnotic, whereas the second group merely showed the residual effects of the drugs.

Adult↗

[The influence of dopamine on hemodynamics, microcirculation and renal function in patients with hypnotic drug intoxication (author's transl)].

The effect of dopamine on hemodynamics (CO, AoPm, TPR, SV, SW, CVP, PAPm, PAEDP), microcirculation (MBF, PS-product) and renal function (VU, CKI, CNa, CK, Cosm, TcH2O) was studied in 8 patients with hypnotic drug poisoning. With increasing doses of dopamine, cardiac output and heart rate increased and the peripheral resistance decreased. An augmentation of stroke volume and left ventricular stroke work was observed in the low dose range only (200--400 mug/min). With increasing doses, central venous pressure as well as mean pulmonary artery pressure and enddiastolic pulmonary artery pressure decreased. No vasoconstriction was found in muscle tissue vessels even with large doses of dopamine. This is explained by the vasoplegic properties of hypnotic drugs. In circulatory shock associated with hypnotic drug poisoning, dopamine develops only minor pressure effects in contrast to its action in circulatory shock of cardiogenic or septic shock origin. High doses of dopamine result in a significant increase in heart rate, without concomitant increase in stroke volume and blood pressure. Therefore the dosage of dopamine should not exceed 400 mug/min in these cases. A combination with small doses of norepinephrine (10--20 mug/min) seems to be more effective. Renal function tests showed variable expansion of urine volume, glomerular filtration rate, and clearances of sodium, potassium and osmotic substances. Therapy with dopamine might increase the renal elimination rate of hypnotic drugs.

Adolescent↗

Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats.

RATIONALE: New sleep disturbance model in rats is useful for estimating the characteristics of some hypnotics. OBJECTIVES: The present study was undertaken to investigate the utility of a sleep disturbance model by placing rats on a grid suspended over water using three kinds of hypnotics, that is, short-acting benzodiazepine (triazolam), intermediate-acting benzodiazepine (flunitrazepam) and long-acting barbiturate (phenobarbital). METHODS: Electrodes for measurement of EEG and EMG were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-REM and REM sleep were measured from 0900 to 1500 hours. RESULTS: In rats placed on the grid suspended over water up to 1 cm under the grid surface, not only triazolam but also flunitrazepam and phenobarbital caused a shortening of sleep latency. Both flunitrazepam and phenobarbital were effective in increasing of total non-REM sleep time in rats placed on sawdust or the grid, and the effects of both drugs in rats placed on the grid were larger than those in rats placed on sawdust. Measurement of the hourly non-REM sleep time was useful for investigating the peak time and duration of effect of the three hypnotics. Phenobarbital showed a decrease in total REM sleep time in rats placed on the grid, although both triazolam and flunitrazepam were without effect. CONCLUSIONS: The present insomnia model can be used as a sleep disturbance model for testing not only the sleep-inducing effects but also the sleep-maintaining effects including non-REM sleep and REM sleep of hypnotics.

Analysis of Variance↗

Behavioral characterization of acetaldehyde in C57BL/6J mice: locomotor, hypnotic, anxiolytic and amnesic effects.

RATIONALE: Acetaldehyde, the first metabolite of ethanol, was recently suggested to contribute to many behavioral effects of ethanol, although few studies have directly investigated the behavioral effects of acetaldehyde itself. OBJECTIVES: The aim of the present study was to characterize the locomotor, hypnotic, anxiolytic-like and amnesic effects of acetaldehyde in C57BL/6J mice. METHODS: Increasing doses of acetaldehyde (0-300 mg/kg) were injected intraperitoneally and their effects on a series of representative behaviors were investigated. The locomotor effects of acetaldehyde were measured in activity boxes. The duration of the loss of righting reflex was used as an index of the hypnotic effects of acetaldehyde. The anxiolytic-like effects of acetaldehyde were tested with an elevated plus-maze and the amnesic effects with the one-trial passive avoidance test. Finally, brain and blood acetaldehyde concentrations were assessed. RESULTS: Acetaldehyde induced a significant hypolocomotor effect at 170 mg/kg and higher doses. In addition, the hypnotic effects of acetaldehyde were demonstrated by a loss of righting reflex after the administration of 170 and 300 mg/kg acetaldehyde. The elevated plus-maze showed that acetaldehyde does not possess anxiolytic-like properties. Finally, acetaldehyde (100-300 mg/kg) dose-dependently altered memory consolidation as shown by a reduced performance in the passive avoidance test. CONCLUSIONS: The present results show that acetaldehyde induces sedative, hypnotic and amnesic effects, whereas it is devoid of stimulant and anxiolytic-like properties in C57BL/6J mice. However, the behavioral effects of acetaldehyde after intraperitoneal administration were apparent at very high brain concentrations. The present results also indicate that acetaldehyde is unlikely to be involved in the anxiolytic properties of ethanol in mice.

Acetaldehyde↗

Correlation of the hypnotic potency of benzodiazepines with inhibition of voltage-dependent calcium uptake into mouse brain synaptosomes.

Nine benzodiazepines were tested for their ability to inhibit 45Ca2+ uptake into mouse whole brain synaptosomes and for hypnotic activity as indicated by their ability to produce loss of the righting reflex. Eight of the benzodiazepines significantly inhibited fast-phase voltage-dependent 45Ca2+ uptake and five exhibited hypnotic activity. There was a direct correlation between the hypnotic potency of these five benzodiazepines and their ability to inhibit 45Ca2+ uptake. There does not appear to be a correlation between the anticonvulsant potency of the benzodiazepines and their potency for inhibiting 45Ca2+ uptake. These results support previous findings with other sedative/hypnotic drugs and suggest that inhibition of presynaptic calcium uptake may be linked with hypnotic but not anticonvulsant actions of benzodiazepines.

Animals↗

Ultradian dynamics of sleep after a single dose of benzodiazepine hypnotics.

A single bedtime dose of the benzodiazepine hypnotics, flunitrazepam (2 mg), triazolam (0.5 mg) or flurazepam (30 mg), was administered to young, healthy subjects. Abortive first rapid eye movement sleep (REMS) episodes, characterized by a low level of EEG slow-wave activity (spectral power density in the 0.75-4.5 Hz band) without rapid eye movements and/or muscle atonia, were more frequent in the drug night than in the placebo night or in the drug-free night following upon the drug night. The benzodiazepine hypnotics depressed slow-wave activity in non-REM sleep (NREMS) in the drug night and the subsequent drug-free night. However, the typical declining trend of slow-wave activity over the first three NREMS-REMS cycles, and the cyclic ultradian pattern of slow-wave activity were little affected by the hypnotics. The results indicate that benzodiazepine hypnotics depress the generation of slow EEG waves without disrupting the homeostatic and ultradian processes of sleep regulation.

Activity Cycles↗

Hypnotic action of benzodiazepines: a possible mechanism.

The objective of this investigation was to determine whether the effects of muscimol on benzodiazepine receptor binding relate to the hypnotic activity of nine benzodiazepines (clonazepam, triazolam, diazepam, flurazepam, nitrazepam, oxazepam, temazepam, clobazam, and chlordiazepoxide) and CL 218,872. There was no correlation between the basal receptor binding affinities of the drugs tested and their hypnotic potencies, whereas the benzodiazepine receptor agonists whose receptor bindings are strongly modulated by muscimol possess potent hypnotic activity. These results indicate that benzodiazepine receptors that couple to GABA receptors are involved in the hypnotic activity of the benzodiazepines.

Animals↗

Hypnotic activity of N3-benzylthymidine on mice.

The pharmacological effect in mice of N3-benzylthymidine (N3-ByTd) was examined by two routes of administration; intravenous (i.v.) and intracerebroventricular (i.c.v.), and compared with the effect of administration of N3-benzyluridine (N3-ByUd) previously reported. Hypnotic activity, pentobarbital (PB)-induced sleeping time, motor incoordination and spontaneous activity were used as indices of pharmacological effects. N3-ByTd (0.5-2.0 mumol/mouse, i.c.v.) and N3-ByUd (1.5-3.0 mumol/mouse, i.c.v.) were found to possess dose-dependent hypnotic activity, and N3-ByTd had more potent hypnotic activity than N3-ByUd. Both N3-ByTd and N3-ByUd (0.5 and 1.0 mumol/mouse, i.c.v., respectively) showed a synergistic effect on PB-induced sleep, although their parent compounds, thymidine (Td) and uridine (Ud), did not potentiate the activity at each dose. In motor incoordination, the effect of N3-ByTd (0.5 mumol/mouse) continued for 6 hr after i.c.v. injection. All compounds decreased the spontaneous activity of mice by i.c.v. administration. Furthermore, both N3-ByTd and N3-ByUd decreased the activity, when they were administered by i.v. These results reveal that both N3-benzylpyrimidine nucleosides have more direct depressant effects on the central nervous system (CNS) than the parent compounds. Among the pyrimidine nucleoside derivatives tested, N3-ByTd was found to be the most potent hypnotic substance.

Animals↗

Protection from shock-induced seizures as a measure of hypnotic potency of drugs.

Mice injected with drug or vehicle were administered a 13 mA shock via corneal electrodes. The number of mice in which the shock produced a tonic seizure was recorded. The dose that blocked seizures in 50% of mice (ED50) was determined for each drug. The drugs evaluated consisted of 15 hypnotics, two antidepressants and two antihistamines. All hypnotics and antidepressants, and one antihistamine, caused a dose-dependent suppression of seizures. The ED50's were highly correlated with hypnotic potency in man. The advantages of this procedure, as compared to others currently used for the evaluation of hypnotic potential of novel compounds, are discussed.

Animals↗

New hypnotic agents: clinical studies in general practice.

The type of sleep problem should be determined so that the most appropriate hypnotic can be used, and in this respect duration of action is an important property. The benzodiazepine hypnotics are adequate for this purpose, but problems may arise due to daytime after-effects and the possibility of dependence developing. Non-benzodiazepine hypnotics may be useful alternatives and our group has undertaken double-blind comparative trials with two such compounds, namely zopiclone and zolpidem. Zopiclone was compared to temazepam in a cross-over trial on 36 patients and similar hypnotic effects were recorded. In a parallel group study, zolpidem 10 mg was compared to zolpidem 20 mg and placebo in 88 patients. Both doses of zolpidem were significantly better than placebo on a number of the parameters recorded, side-effects were negligible and there was no evidence of any rebound insomnia during the final control week.

Clinical Trials as Topic↗

Sedative-hypnotic drugs and the risk of hip fracture.

A retrospective cohort study was conducted in individuals 65 years of age and older using Medicaid-reimbursed claims to assess the risk of hip fracture in users of two sedative-hypnotic drugs, triazolam and temazepam. Using the triazolam cohort as the referent group, the rate ratio was 0.92 (95% confidence interval, 0.72 to 1.17) for hip fracture with temazepam. Stratifying by age, sex, race, residence, time enrolled in Medicaid, prescription number, combinations of these, and several other potential confounding variables did not materially change the results. Compared with the short-acting benzodiazepine hypnotic temazepam, use of triazolam, an ultra-short-acting benzodiazepine hypnotic, did not decrease the risk of hip fracture. This study did not determine that either drug, compared with no use in an insomniac control group, increases the risk of hip fracture. However, because sedative-hypnotic drugs have been found in other studies to increase the risk of falling and hip fracture, they should be used with caution, especially in the elderly.

Accidental Falls↗

Effects of short-acting hypnotics on sleep latency in rats placed on grid suspended over water.

The present study was performed to develop a new sleep disturbance model for evaluating hypnotic potencies by placing rats on a grid suspended over water up to 1 cm under the grid surface. When rats were placed on the grid, significant increases in sleep latency and amount of wakefulness were observed compared with those of rats placed on sawdust. However, the amounts of non-rapid eye movement (non-REM) sleep and rapid eye movement (REM) sleep of rats placed on the grid were significantly decreased compared with those of rats placed on sawdust. Four short-acting hypnotics (triazolam, zopiclone, brotizolam, lormetazepam) caused significant decreases in sleep latency, and the effects of hypnotics in rats placed on the grid were more potent than those in rats placed on sawdust. In conclusion, the present model can serve as a new sleep disturbance model and may also be useful for evaluating the sleep-inducing effects of short-acting hypnotics.

Animals↗

Effects of hypnotics on the sleep EEG of healthy young adults: new data and psychopharmacologic implications.

Benzodiazepine hypnotics increase NREM sleep and alter its EEG by reducing delta (0.3-3 Hz) and increasing sigma (12-15 Hz) and beta (15-23 Hz) activity. We tested whether the nonbenzodiazepine hypnotic, zolpidem (10 mg), produced the same pattern of sleep and EEG changes as two "classical" benzodiazepines, triazolam (0.25 mg) and temazepam (30 mg). Sleep EEG of 16 subjects was analyzed with period amplitude analysis for 3 nights during drug administration or placebo. The effects of zolpidem were in the same direction but generally of smaller magnitude than those of the classical benzodiazepines. These differences are more likely the result of non-equivalent dosages than different pharmacologic actions. Period amplitude analysis showed that the decreased delta activity resulted mainly from a decrease in wave amplitude. In contrast, the increased sigma and beta activity were produced by increased wave incidence. Delta suppression increased with repeated drug administration but sigma and beta stimulation did not. While these findings have little relevance for the clinical choice of hypnotics they may hold important implications for the brain mechanisms involved in hypnotic tolerance and withdrawal delirium.

Adult↗

Anxiolytic and hypnotic use by general hospital inpatients. The impact of psychopathology and general medical conditions.

This study explored the relative impact of general medical conditions and psychopathology on the current and lifetime use of anxiolytic and/or hypnotic drugs by general hospital inpatients. One hundred and five consecutive patients, admitted to an internal medicine department, were assessed by a structured interview about current and lifetime use of anxiolytic and/or hypnotic drugs, and with somatic and psychopathology scales. Eighty percent of patients reported using anxiolytics and/or hypnotics at least once in a lifetime, 62.9% in the last year, 55.2% in the last 3 months, and 42.9% in the last week. Correlations were found between drug use and current levels of anxiety and depression, but not somatic pathology. Psychological suffering appeared to be a major determinant for anxiolytic and/or hypnotic use by patients with general medical conditions. Consumption rates were higher than in the general population, but there was no direct link between somatic morbidity and drug use.

Adolescent↗

Association between use of sedatives or hypnotics, alcohol consumption, or other risk factors and a single injurious fall or multiple injurious falls: a longitudinal general population study.

In this study, we investigated the association between risk factors, including use of sedatives or hypnotics or alcohol consumption, and injurious falls leading to hospitalization or death among 4023 subjects (1828 men and 2195 women) aged 20-89 years in Stockholm County, Sweden. Questionnaire data obtained from the 1984-1985 Stockholm Health of the Population Study (SHPS) were linked to official data registers on hospitalization and mortality. Of the 4023 subjects, 330 (121 men and 209 women) had been treated for or died of injurious falls during the 12-year follow-up period. High age was significantly associated with injurious falls among both men and women. Multivariate analyses showed that women who had used sedatives or hypnotics during the 2 weeks before an injurious fall were at increased risk [relative risk of 1.83 (95% confidence interval, 1.10-3.06)] for two or more injurious falls, but not for a single fall accident. High alcohol consumption and earlier self-reported injurious falls were significantly associated with injurious falls for women younger than 60 years of age and with earlier self-reported falls and living alone for men in the same age category. Among older women (>60 years of age), high alcohol consumption and use of sedatives or hypnotics were significantly associated with injurious falls, whereas living alone and earlier self-reported accidents were significant predictors for men in the same age category. These results support a cautious prescribing policy for sedatives and hypnotics, as well as an awareness of high alcohol consumption and its association with injurious falls.

Accidental Falls↗

Hypnotic action of melatonin during daytime administration and its comparison with triazolam.

The present study was conducted to assess hypnotic action, effects on rectal temperature and dose dependency by daytime administration of exogenous melatonin (MLT) at 1 mg, 3 mg or 6 mg to subjects consisting of seven healthy juvenile adults. As a result, exogenous MLT significantly increased total sleep time and sleep efficiency, and MLT 6 mg was observed to demonstrate hypnotic effects that were nearly equal to those of triazolam at 0.125 mg. Rectal temperature was significantly decreased at MLT 1mg and 3 mg, there were no significant differences observed in the hypothermic effects at MLT 6 mg. These results indicate that exogenous MLT had dose-dependent hypnotic action on daytime sleep, and it is possible to consider that this hypnotic action was based on a direct-acting mechanism.

Adult↗