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PubMed1979

Comparison of a new hypnotic (Finorgal) with placebo in a double-blind trial.

The hypnotic effects of Finorgal (ethchlorvynol with diphenhydramine) were compared with those of placebo in a double-blind study with crossover of treatments in thirty-five hospital in-patients. During the four-week period of Finorgal treatment there was a significant reduction in the mean time elapsing between the administration of the hypnotic and the onset of sleep, and a significant increase in the duration of sleep, compared with the four weeks of placebo treatment. There was also a significant increase in the proportion of nights when the patients felt they had slept well, and in the incidence of morning 'hangover' and nocturnal confusion during the Finorgal treatment periods. Patients had to be actively woken in the morning significantly more often following Finorgal administration. In patients experiencing pain in the night there was a significant reduction in the occurrence of pain during the nights when Finorgal had been given.

Adolescent↗
PubMed1999

Zolpidem, a valuable alternative to benzodiazepine hypnotics for chronic insomnia?

Sleep quality and anxiety levels were examined using questionnaires and polysomnographic recordings in 22 chronic insomnia patients who regularly used benzodiazepines to treat their sleeping problems. After abruptly discontinuing their benzodiazepine medication, patients were randomly allocated to receive either a placebo or zolpidem 10 mg for 1 week, after which they entered an open extension phase, receiving zolpidem 10 mg for 3 weeks. Subjectively, sleep quality was considered mediocre during the use of a benzodiazepine hypnotic. One week after the discontinuation, an increase in sleep latency was observed in the placebo group, whereas zolpidem induced a significant decrease in sleep latency. Deterioration of other sleep variables (probably rebound) was not suppressed by zolpidem. An explanation for this could be the selective pharmacological profile of zolpidem. Polysomnographic differences between placebo and benzodiazepine and between placebo and zolpidem were not reflected by the subjective data on sleep and anxiety. Changes of sleep structure caused by hypnotics seem not always to be felt as such by patients. After 3-4 weeks of zolpidem treatment, the percentage of non-rapid eye movement-4 sleep increased significantly, corresponding with a significant subjective improvement of sleep quality. This indicates that zolpidem may restore physiological sleep.

Adult↗
PubMedDate not supplied

A comparison between chlormethiazole and nitrazepam as hypnotics in psycho-geriatric patients.

A double-blind crossover study was carried out in 68 demented elderly patients (mean age 77 years) to compare the hypnotic effects of chlormethiazole and nitrazepam. Chlormethiazole was administered as a 5% mixture (500 mg. chlormethiazole edisylate) in a 10 ml. dose: the corresponding single dose of nitrazepam was 10 mg. Treatment was discontinued in 6 patients and interrupted for from 1 to 3 days in a further 18 due to side-effects and 'hang-over' problems or because of intercurrent infections. Of these 24 drop-outs, 3 occurred during chlormethiazole treatment (1 severe 'hang-over'; 2 refused to take medication) and 21 during nitrazepam (15 severe 'hang-over' effects, including sleepiness and muscular weakness; 2 nausea; 4 intercurrent infection). Both preparations were equally effective as hypnotics, there being no noteworthy differences in time of onset or in duration of sleep. Of the 44 patients completing the trial without interuption, observations were carried out for 308 nights on each preparation. Chlormethiazole patients slept for more than 6 hours on 244 of the 308 nights without 'hang-over' effect the next day compared with 163 out of 308 nights of those on nitrazepam. The difference is statistically significant in favour of chlormethiazole. The high incidence of 'hang-over' effect during nitrazepam treatment indicates that a single 10 mg. dose is too large for use in the elderly. Overall assessment of treatment was made in 62 patients. Chlormethiazole was judged to be the most suitable drug in 37, nitrazepam in 11, and both preparations equally useful in the remaining 14 patients. This difference is statistically significant.

Aged↗
PubMed1991

Acute tolerance to the hypnotic effect of morphine in rats.

To demonstrate the development of acute tolerance to the hypnotic effects of morphine, loss and recovery of the righting reflex with a constant-rate morphine infusion was studied in rats. In one group of animals, brain and serum concentrations of morphine were detected (radioimmunoassay) at the time of loss of the righting reflex, and in another group, at the time of the reflex recovery. The morphine infusion at a constant rate of 14 mg.kg-1.h-1 caused a loss of the righting reflex in all animals that was achieved by 2.5 h. However, this level of response could not be maintained, and at 5 h it began to decline. All animals recovered the righting reflex by the ninth hour, despite the continuing morphine infusion. The morphine brain and serum levels at the times of loss and recovery of the righting reflex were not different. The results suggest a development of acute tolerance to the hypnotic effect of morphine, which is determined primarily by pharmacodynamic mechanisms.

Animals↗
PubMed2003

The hypnotic and analgesic effects of 2-bromomelatonin.

2-bromomelatonin is an analog of melatonin with a higher melatonin receptor affinity. We tested the hypnotic and analgesic properties of 2-bromomelatonin and compared them with those of propofol. Sprague-Dawley rats were assigned to receive 2-bromomelatonin or propofol IV, or morphine intraperitoneally. Righting reflex and response to tail clamping were assessed. Both 2-bromomelatonin and propofol caused a dose-dependent increase in the percent of rats displaying loss of both the righting reflex and the response to tail clamping. 2-Bromomelatonin was comparable to propofol in terms of its rapid onset and short duration of hypnosis. The 50% effective dose (95% confidence interval) for loss of righting reflex for propofol and 2-bromomelatonin were 3.7 (3.4-4.0) and 38 (35-41) mg/kg, respectively. Corresponding values for loss of response to tail clamp were 2.9 (3.5-4.0) and 21 (15-30) mg/kg, respectively. 2-bromomelatonin is approximately 6-10 times less potent than propofol depending on the end-point used. Intraperitoneal 30 mg/kg morphine did not affect the righting reflex, but resulted in loss of response to tail clamping in all animals. 2-bromomelatonin can exert hypnotic and antinocifensive effects similar to that observed with propofol. Unlike propofol, the reduced nocifensive behavior persisted after the animals had regained their righting reflex. This study provides evidence that 2-bromomelatonin has properties that are desirable in anesthetics or anesthetic adjuvants.

Analgesics, Non-Narcotic↗
PubMed2005

The dosing-time dependent effects of intravenous hypnotics in mice.

Chronobiology, which focuses on the biological rhythms that occur in the organization of living organisms, has been studied for several decades. Chronopharmacology, however, has received little attention until recently. We examined the hypnotic duration of intraperitoneally administered ketamine, pentobarbital, propofol, midazolam, and ethanol, to test whether they have obvious dosing-time dependent effects. Male C57BL/6 mice, which showed clear circadian rhythms of water-intake under a strict 12-h lighting cycle, were used. All tested drugs had significantly longer episodes of loss of righting reflex when administered at 22:00 (early active phase) than at 10:00 (early inactive phase). This dosing-time dependent hypnotic duration did not depend on the contents and activities of cytochrome P450 enzymes in the liver. These findings might be of clinical benefit in deciding the administration time and doses of anesthetics.

Animals↗
PubMed2005

Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.

In the present study, we investigated hypnotic activities of chamomile and passiflora extracts using sleep-disturbed model rats. A significant decrease in sleep latency was observed with chamomile extract at a dose of 300 mg/kg, while passiflora extract showed no effects on sleep latency even at a dose of 3000 mg/kg. No significant effects were observed with both herbal extracts on total times of wakefulness, non-rapid eye movement (non-REM) sleep and REM sleep. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3 mg/kg showed a significant antagonistic effect on the shortening in sleep latency induced by chamomile extract. No significant effects were observed with chamomile and passiflora extracts on delta activity during non-REM sleep. In conclusion, chamomile extract is a herb having benzodiazepine-like hypnotic activity.

Animals↗
PubMed1982

Alteration of convulsive threshold and sensitivity to CNS acting drugs in sedative-hypnotics-experienced rat offspring.

The present study was made to investigate the developmental toxicity of ethanol and several sedative-hypnotics (barbital, diazepam, phenobarbital) administered to rat pups via dams for 18 days (day 3-21 after parturition) from the relatively early postnatal stage in terms of changes in the threshold for pentetrazol (PTZ)-induced convulsion, tolerance to, and physical dependence on barbital (B). In the pups of all dosed groups, the convulsive threshold for PTZ is reduced significantly compared with that in the naive group. The sleeping time with B in phenobarbital-exposed offspring was also reduced significantly compared with that in the naive pups. No difference was however, noted in the B concentration of the brain or plasma upon awaking between these groups of pups, which proved that the phenobarbital-exposed pups had obviously acquired a functional tolerance to B. B-dependence formation and the ensuring weight loss and appearance of withdrawal signs, especially clonic-tonic convulsion, were made intense in the phenobarbital-experienced pups. From these results, it may be concluded that exposure to sedative-hypnotics from the early CNS developing stage makes a lowered state of convulsive threshold for PTZ, and therefore, tends to enhance B-withdrawal convulsion. These phenomena were discussed from the viewpoint of monoamine metabolism in the brain.

Animals↗
PubMed1990

Abuse liability of barbiturates and other sedative-hypnotics.

The principal action of the sedative-hypnotic drugs, of whom the barbiturates are the most widely known and utilized, is to produce drowsiness and promote sleep. At one time these were also the only drugs available to calm seriously anxious or disturbed people. Unfortunately, in addition to their clinical applications these drugs manifest a very high abuse potential. Experienced drug abusers report feelings of well-being and euphoria while under the influence of these drugs. Self-administration experiments conducted in animals have shown that the barbiturates are potent reinforcing agents. In controlled studies in humans, former drug abusers express a preference for barbiturates over benzodiazepines and will "work" to receive barbiturates. Long term consumption of the sedative-hypnotics, particularly barbiturates, leads to dependence characterized by a severe, potentially life-threatening abstinence syndrome following the abrupt withdrawal of the drug. Withdrawal manifestations include delirium and grand mal seizures. Because of the high abuse potential of these drugs, their manufacture and distribution has been greatly curtailed, and for most clinical applications they have been largely replaced by drugs, e.g., the benzodiazepines, which appear to have much less abuse liability.

Animals↗
PubMed2005

Indiplon: the development of a new hypnotic.

Indiplon is a short-acting hypnotic that is currently being developed as a treatment for insomnia by Neurocrine Biosciences and Pfizer, and is expected to be marketed in mid-2006. It is a high-affinity allosteric potentiator of GABAA responses that demonstrates preference for alpha1 subunit-containing GABAA receptors. Indiplon will be an addition to the general category of newer-generation hypnotics that now includes zaleplon, zolpidem, zopiclone and eszopiclone. Clinical trials were carried out with an immediate-release capsule and a modified-release tablet and demonstrate very positive efficacy and safety profiles. The major challenge will be developing a commercial success in the crowded insomnia treatment marketplace.

Animals↗
PubMed2006

Emerging pharmacotherapeutic agents for insomnia: a hypnotic panacea?

The burden of insomnia has had a significant effect not only on the socioeconomic matrix, but also the medical terrain, as signified by the increased morbidity and mortality of its associated psychiatric and organic sequelae. To this end, a plethora of pharmacotherapeutic agents have been recently introduced that address the vital need to combat insomnia and prevent the perpetuation in its chronic form. The previously and currently dispensed barbiturates and benzodiazepines, respectively, have paved the way for newer agents that are purported to be just as effective, or even more so, with a favourable profile in all domains of sleep. In assessing both published clinical studies and unpublished reports conducted on these emerging agents, this article profiles the most contemporary, therapeutic options in lieu of older hypnotics, over-the-counter medications and supplements. Furthermore, this paper aims to indicate both the future course of hypnotics and the developments currently in progress.

Humans↗
PubMed1983

Effects of barbiturates and other sedative hypnotics in pigeons trained to discriminate phencyclidine from saline.

Pigeons were trained to peck the center key (lighted white) of three response keys to turn off the center keylight and to light one of the side keys with a red keylight and the other side key with a green keylight. Five responses (fixed-ratio component) on either side key relighted the center key. Food was delivered following 10 fixed-ratio components on the red key if 1.5 mg/kg phencyclidine had been given before the session. The position of the red and green keylights on the side keys varied randomly each time they were lighted by a peck on the center key. Subsequently, increasing doses of phencyclidine, barbital, amobarbital, phenobarbital, methaqualone, methyprylon, diazepam, oxazepam, and d-amphetamine were substituted for the training dose of phencyclidine, using a cumulative dosing procedure. At low doses of the sedative hypnotics, birds pecked the keylight color associated with saline. At higher doses, birds pecked both key colors. At the highest doses of pentobarbital and amobarbital, some birds responded almost exclusively On he color associated with phencyclidine. When responding on keys of both colors occurred following administration of phencyclidine or other sedative hypnotics, this responding was controlled by key position rather than by key color.

Animals↗
PubMed1994

Patterns of sleep disorders and sedative hypnotic use in seniors.

Adequate sleep is required for good physical and psychological health. Sleep disturbance is common and its prevalence increases with advancing age. Physiologically, sleep in elderly adults differs from that in younger adults, both in terms of quantity and quality. Sleep disturbance in old age may be associated with many physical and psychological conditions, and less commonly can occur as a primary disturbance. It must be distinguished from the understandable but unrealistic expectations of many elderly people that they will sleep for as long and as soundly as when they were younger. The evaluation of a patient with a sleep disorder requires full medical psychiatric and social histories, mental state and physical examinations and appropriate investigations. If present, an underlying condition should be treated. Management strategies for sleep disorders include attention to sleep hygiene, behavioural treatment and hypnotics. Ideally, a hypnotic should be prescribed for a limited period and then in the smallest effective dose.

Aged↗
PubMed1996

Hypnotics. Drug selection by means of the System of Objectified Judgement Analysis (SOJA) method.

Selection of hypnotics for drug formularies in The Netherlands, France and the UK is made by means of the System of Objectified Judgement Analysis (SOJA) method. The following criteria are included in the method: clinical efficacy (maximal 300 points), adverse effects (250 points), clinical documentation (150 points), cost (120 points), pharmacokinetic properties (80 points), toxicity (50 points), drug interactions (30 points) and the number of tablet strengths available (20 points). In all 3 countries, zolpidem, zopiclone and temazepam showed the highest score, followed by lormetazepam. High scores favour inclusion in formularies. Nitrazepam and loprazolam scored 75 to 130 points less than the top 3, and flunitrazepam shows the lowest score (119 to 183 points less than zolpidem, zopiclone and temazepam). Therefore, the first 3 (or 4) hypnotics are most suitable for formulary inclusion while the others are not.

Humans↗
PubMed1980

Field dependence in patients with exclusive abuse of hypnotics or sedatives.

A group of 47 patients exclusively abusing sedatives-hypnotics (not alcohol or hard drugs) has been studied with regard to field dependence as assessed by a rod-and-frame test. In comparison to a pairwise matched control group from the general population these sedative-hypnotic abusers were not more field dependent, even though they in a previous study were shown to have a higher incidence of intellectual impairment.

Adult↗
PubMed1979

Self-poisoning with over-the-counter hypnotics.

Over-the-counter (OTC) hypnotic preparations (such as Sominex, Nytol, and Sleep Eze) were implicated in 21 of the 773 admissions to Massachusetts General Hospital due to psychotropic drug overdosage between 1962 and 1975. Ten of the 21 cases had manifestations of central anticholinergic toxicity ("atropine-like psychosis"), such as hallucinations, delirium, and confusion. However, all patients recovered rapidly and without sequelae. Specific therapy (i.e., physostigmine) was rarely required. Thus OTC hypnotic overdosage commonly produces "toxic psychosis." Fortunately, intoxication is usually of short duration and relatively benign.

Adolescent↗
PubMed2000

The treatment of sedative-hypnotic dependence: evaluating clinical predictors of outcome.

BACKGROUND: The objectives of this 6-month prospective study were to evaluate the efficacy of detoxification treatment for sedative-hypnotic dependence, examine the demographic and clinical predictors of outcome, and determine whether anxiety or other psychiatric comorbidity has a negative impact on outcome. METHOD: Eighty-two patients with alcohol or benzodiazepine dependence (DSM-IV diagnostic criteria) were consecutively recruited upon entering treatment and were assessed by clinical and semistructured interviews, the Global Assessment Scale, the Hamilton Rating Scale for Depression, the Beck Depression Inventory, the revised 90-item Symptom Checklist, and urine drug screening. RESULTS: Both alcohol- and benzodiazepine-dependent patients succeeded in reducing their reported use of sedative-hypnotic substances during the follow-up period. However, at 3 months, benzodiazepine-dependent patients fared less well than alcohol-dependent patients in terms of several outcome measures: they reported a lower rate of achieving abstinence, shorter periods of continuous abstinence, and more frequent drug use. At 6 months, the differences in outcome among the drug groups were not maintained. Variables such as sex, drug group, and indicators of psychiatric status had little impact on outcome measures. Benzodiazepine-dependent patients reported significant decreases in their level of anxiety over the follow-up period despite substantial reductions in benzodiazepine use. CONCLUSION: Clinicians may be encouraged regarding the detoxification of patients who have used benzodiazepines at high doses or for long periods of time, or who have comorbid anxiety or other psychiatric disorders.

Adult↗
PubMedDate not supplied

[Determination of the retention indices (Rf) of hypnotic and anticonvulsant sedatives by thin layer chromatography using Merck silica gel plates (author's transl)].

In view of the sometimes considerable differences between absolute retention indices (Rf) given in the literature even with the same solvent, same type of adsorbent layer and same operating temperature, the Author proposes the adoption of a standard method derived from the analytical repeatability of Rf values on a thin layer; this would provide a means of searching for a specific parameter by which to identify whole categories of drugs, classified according to their primary therapeutic activity. The study here covers numerous items in the category of hypnotic and anticonvulsant sedatives (barbiturates, non-barbiturate hypnotic drugs, hydantoins, suxinimides, and anticonvulsant agents with various different structures.

Anticonvulsants↗