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[Deep cerebral electrical activity during the hypnotic state in man: neurologic considerations in hypnosis].

To the authors' knowledge hypnosis has never been induced in epileptic patients during depth EEG study. This neurosurgical diagnostic procedure (that has been routinely used in medically resistant epileptic patients for the preoperative exact delimitation of the epileptogenic lesion) offers a unique opportunity of obtaining fundamental information on the possible neurophysiological mechanisms implied in human hypnosis. Observations were carried out on 3 consecutive patients affected by medically resistant partial seizures with elementary and/or complex symptomatology. A chronic deep electrode study explored rhinencephalic structures as well as specific target areas of the cerebral cortex. Background electrical activity during the hypnotic state showed a significant decrease of slow waves and an increase of alpha and beta rhythms, with constant increase of amplitude, as compared with the nonhypnotic state. Focal interictal abnormalities were drammatically reduced by hypnotic trance. Moreover, depth EEG study during sleep in one patient indicated that the EEG patterns during hypnosis and sleep are basically different, confirming that there is no convincing evidence of physiological similarities between the 2 states.

Adult↗

[Use of hypnotism in transcutaneous renal biopsy. Preliminary results].

We wish to point out the outstanding importance of kidney biopsy in diagnosis of kidney diseases and enphasize the fact that it is very important for the patient to give one's full cooperation, in order to achieve the most successful results. Anxious subjects and children usually do not give this cooperation owing to their excessive emotional reactions to the special situation of the biopsy and so we think it useful to induce beforehand a hypnotic state in them, hoping that this would make it possible to carry out the research with the usual transcutaneous technique. In this research, which is to be considered as preliminary, ten patients were examined, nine of whom aged from three to fourteen and one aged forty-six. Eight subjects, out of ten, reached such a degree of hypnotic depth that it was possible to carry out the biopsy in a few minutes without noteworthy difficulties. The high ratio of successful cases and the lack of any considerable complications in their experiments enable the Authors, though still waiting for a wider range of data, to suggest since now the use of hypnosis whenever the patients prove reluctant to cooperation.

Adolescent↗

Double-blind evaluation of the safety and hypnotic efficacy of lormetazepam in general practice.

The efficacy and safety of lormetazepam (LMZ) and placebo were compared in 30 patients with sleep difficulties who were treated by general practitioners. During the three weeks of the study, each patient received placebo during either the first or last week and 1 mg/night of LMZ during the other two weeks. Neither patients nor physicians knew which week's medication was active drug and which was placebo. Twenty-three of the 30 patients completed the three-week trial. Both the quantity and the quality of sleep were significantly better during the weeks patients were given LMZ than during the week they used placebo. Physicians also rated the hypnotic performance as significantly better than that of placebo. Adverse reactions were evenly distributed among the LMZ and placebo treatment periods and were usually minor. Vital signs and laboratory values were unchanged during either treatment period. It is thus concluded that LMZ is a safe and effective hypnotic for use in general practice.

Adolescent↗

Comparative hypnotic effects of flurazepam, triazolam, and placebo: a long-term simultaneous nighttime and daytime study.

We studied sleep and daytime function in insomniac patients who took either flurazepam, 30 mg, triazolam, 0.5 mg, or placebo 30 minutes before bedtime. Subjects were 21 patients with either a primary or a secondary diagnosis of chronic psychophysiological insomnia or insomnia associated with personality disorder. Seven subjects were randomly assigned to each condition. The study used a three group by 9 week, double-blind design with three nocturnal sleep recordings each week. During week 1, subjects took no capsules; week 2, subjects took placebo; weeks 3 to 7, flurazepam, triazolam, or placebo; weeks 8 and 9, placebo. Daytime tests for alertness and performance were administered during weeks 1, 3, 5, 7, and 8. Flurazepam showed hypnotic efficacy for weeks 3 to 5. Triazolam showed hypnotic activity for weeks 3 to 7. Although not significant overall, discontinuation of flurazepam produced rebound insomnia in six of seven subjects sometime during the two withdrawal weeks. The relationship between plasma concentration of desalkylflurazepam, the principal active metabolite of flurazepam, and sleep disturbance suggested that the onset of the rebound insomnia depended on the rate of drug washout. Discontinuation of triazolam produced a significant rebound insomnia on the first and second nights of drug withdrawal. Placebo subjects showed improved sleep throughout weeks 2 to 9 of the study. Daytime testing revealed significantly decreased daytime alertness and decreased performance for flurazepam subjects during weeks 3 to 7, although these effects reverted toward baseline despite continued drug administration.

Adult↗

An evaluation of the short-term hypnotic efficacy of loprazolam in comparison with nitrazepam in elderly patients.

A double-blind, parallel group, randomized trial was carried out to compare the hypnotic efficacy of 1.0 mg loprazolam and 5.0 mg nitrazepam in 40 elderly patients. All had disturbed sleep patterns, which were not the result of physical illness, and had been shown to be placebo non-responders during a 3-day placebo screening period. Patients received active medication for 7 nights. Both loprazolam and nitrazepam significantly improved sleep patterns, as measured by patient self-rating scales and night nurses' global assessments, in comparison with the placebo baseline screen (p less than 0.001). No significant differences in efficacy were shown between drug treatments and no untoward effects were recorded which could be attributed to either drug. The results suggest that 1.0 mg loprazolam is an effective and well-tolerated hypnotic in elderly patients suffering from insomnia.

Aged↗

[Hypotheses on the psychodynamics of the hypnotized].

The hypnotic process starts when the ties between subject and object (perceptions) are sufficiently slackened. The psychodynamics of hypnosis in the hypnotized are reviewed, highlighting the mental machinery set in motion from the start of the process to its conclusion.

Dissociative Disorders↗

[Metacommunication in waking and hypnotic states].

A definition is given of the terms "communication" and "metacommunication", "language" and "metalanguage", and the several types of relationships that may arise in communication: "symmetrical competitive", "integrative complementary", "metacomplementary", and "paradoxical", Reference is made to the "spontaneity" and "simulation" that may arise in communication and metacommunication, during both wakefulness, conscious states in barbituric subnarcosis, and hypnosis. The question of metacommunication during the induction of hypnosis and during the hypnotic relationship is examined, stress being placed on the parapsycholgical metacommunications that may take place during some forms of self- or hetero-induced hypnotic consciousness.

Adult↗

Effects of hypnotic suggestions on ultraviolet B radiation-induced erythema and skin blood flow.

Results from both animal and human studies have indicated that inflammatory skin reactions such as the flare response to histamine prick test involve a neurogenic regulatory component. It is still unknown to which degree inflammation induced by ultraviolet (UV) radiation may be mediated by the central nervous system. To investigate this, the effect of hypnotic suggestions to increase and decrease the response to UVB radiation on erythema and cutaneous blood flow was investigated in 10 highly hypnotizable subjects. The results showed a significant effect of hypnotic suggestions on cutaneous blood flow compared with the responses of a control group. For erythema no conclusive evidence was found. The results indicate the possibility of separate regulatory mechanisms behind central nervous system influence on UVB-induced erythema and skin blood flow respectively, and further investigations are needed.

Adult↗

Pharmacological properties of thalidomide (alpha-phthalimido glutarimide), a new sedative hypnotic drug.

Thalidomide (alpha-phthalimidoglutarimide, "Distaval," "Contergan") is a new sedative hypnotic drug which produces no toxic effects when administered orally to animals in massive doses. This lack of toxicity may be due to limited absorption. The drug has a quietening effect on the central nervous system, reducing the voluntary activity of laboratory animals and promoting sleep. Unlike the barbiturate drugs it does not cause an initial excitation in mice, incoordination or narcosis. It potentiates the actions of other central nervous system depressants, in particular the barbiturates. Its sedative effects are counteracted by central nervous system stimulants. It has no deleterious side effects and does not affect the heart, respiration or autonomic nervous system.

Animals↗

Clinical and statistical evaluation of six hypnotic agents.

Six hypnotic drugs and a placebo were coded and administered at random, one dose at 8 p.m., to 20 patients in a Toronto hospital. A special evaluation scale was used, studying average duration of sleep, time of onset of sleep, quality of sleep and side effects. Secobarbital sodium and methyprylon were statistically significantly more effective than the placebo. The other drugs, glutethimide and three quinozolinone derivatives, were not statistically different from the placebo in their effects. The placebo effect itself was studied. A particular feature of this report is the detailed statistical treatment of the data collected.

Glutethimide↗

A CLINICAL EVALUATION OF FOUR HYPNOTIC AGENTS, USING A LATIN-SQUARE DESIGN.

A double-blind study with a Latin-square design was undertaken on 25 elderly patients, using a placebo and four hypnotic drugs: ethchlorvynol 500 mg., glutethimide 500 mg., chloral hydrate 500 mg., and secobarbital sodium 100 mg. The trial lasted for five weeks. The drugs were all effective compared with the placebo, differences in sleeping time being statistically significant. Differences between these four drugs were not statistically significant. Sleep was induced soonest by secobarbital and ethchlorvynol. Ethchlorvynol and glutethimide had a relatively somewhat longer period of activity than the others. Glutethimide produced most side effects, especially morning drowsiness. Ethchlorvynol and chloral hydrate produced relatively few cases of drowsiness.

Aged↗

Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects.

CONTEXT: Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist recently approved for insomnia treatment. Most approved insomnia medications have potential for abuse and cause motor and cognitive impairment. OBJECTIVE: To evaluate the potential for abuse, subjective effects, and motor and cognitive-impairing effects of ramelteon compared with triazolam, a classic benzodiazepine sedative-hypnotic drug. DESIGN: In this double-blind crossover study, each participant received oral doses of ramelteon (16, 80, or 160 mg), triazolam (0.25, 0.5, or 0.75 mg), and placebo during approximately 18 days. All participants received each treatment on different days. Most outcome measures were assessed at 0.5 hours before drug administration and repeatedly up to 24 hours after drug administration. SETTING: Residential research facility. PARTICIPANTS: Fourteen adults with histories of sedative abuse. MAIN OUTCOME MEASURES: Subject-rated measures included items relevant to potential for abuse (eg, drug liking, street value, and pharmacological classification), as well as assessments of a broad range of stimulant and sedative subjective effects. Observer-rated measures included assessments of sedation and impairment. Motor and cognitive performance measures included psychomotor and memory tasks and a standing balance task. RESULTS: Compared with placebo, ramelteon (16, 80, and 160 mg) showed no significant effect on any of the subjective effect measures, including those related to potential for abuse. In the pharmacological classification, 79% (11/14) of subjects identified the highest dose of ramelteon as placebo. Similarly, compared with placebo, ramelteon had no effect at any dose on any observer-rated or motor and cognitive performance measure. In contrast, triazolam showed dose-related effects on a wide range of subject-rated, observer-rated, and motor and cognitive performance measures, consistent with its profile as a sedative drug with abuse liability. CONCLUSION: Ramelteon demonstrated no significant effects indicative of potential for abuse or motor and cognitive impairment at up to 20 times the recommended therapeutic dose and may represent a useful alternative to existing insomnia medications.

Administration, Oral↗

Anticonvulsant and sedative-hypnotic activities of N-substituted isatin semicarbazones.

A series of N-methyl/acetyl, 5-(un)-substituted isatin-3-semicarbazones were screened for anticonvulsant and sedative-hypnotic activities. The results revealed that protection was obtained in all the screens i.e., MES, scPTZ, and scSTY. Compounds 2, 4, 6, 10 but not 1 and 3 showed low neurotoxicity when compared to clinically used drugs. Compounds 5, 7, 8 and 9 were completely non-toxic. Compound 6 showed good activity in the rat oral MES screen. Among all the compounds, 3 and 6 emerged as the most active compounds as indicated by the protection they exhibit in MES, scSTY, and scPTZ screens. All the compounds showed significant sedativehypnotic activity.

Animals↗

Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy.

Sedative-hypnotic antiepileptic drugs have potentially toxic effects, but their removal is often thought to be difficult and dangerous. We completely withdrew all barbiturates and benzodiazepines from 78 patients with intractable epilepsy (48 inpatients and 30 outpatients). Initially, 19 patients had plasma levels of sedative drugs above the therapeutic range; 28 were taking more than one of these drugs. Dosages of nonsedative antiepileptic drugs were adjusted to provide optimal seizure control. After 6 months of outpatient follow-up, 69 patients remained on a nonsedative regimen: 35 (51%) showed improvement in both drug toxicity and seizure control, 13 (19%) in toxicity alone, 8 (12%) in seizure control alone; 12 (16%) were unchanged, and 1 was worse. Of 9 patients restarted on sedative antiepileptic drugs by their private physicians, 4 had more toxic symptoms than at discharge, 1 had more frequent seizures, 3 were unchanged, and 1, who had had a temporal lobectomy after drug withdrawal, had less frequent seizures. Sedative drugs are not necessary for optimal seizure control, even in intractable epilepsy, and they may be safely withdrawn.

Adolescent↗

[Cyclic ureas. 1. Racemates and enantiomers of hexahydropyrimidine-2-ones: synthesis, configuration and sedative-hypnotic action].

The racemates and the enantiomers of the hexahydropyrimidin-2-ones 2a-2e which can be regarded as cyclic ureas are obtained from the racemates and the enantiomers of the barbiturates 1a-1e by reduction with LiAlH4/AlCl3. The enantiomers of 2a-2d, dextrorotatory in ethanol, possess S-configuration. In a study with rats all cyclic ureas synthesized showed sedative-hypnotic activity. Some of the enantiomers exhibited marked enantioselecive differences in their potency.

Animals↗

[Cyclic ureas. 2. Racemates and enantiomers of imidazolidin-2-ones: synthesis, configuration and sedative-hypnotic action].

The racemates and the enantiomers of the imidazolidin-2-ones 2a and 2b, which can be considered as cyclic ureas, are obtained from the racemates and the enantiomers of the hydantoins 1a and 1b by reduction with LiAlH4/AlCl3. The enantiomers that are dextrorotating in ethanol possess S-configuration. In a study with Wistar-rats, 2a and 2b show sedative-hypnotic activity. The enantiomers exhibit marked enantioselective differences in their potency.

Animals↗

Some analogues of 1,4-disubstituted piperazines as hypnotic and sedative agents.

Preparation, analytical data, and biological properties such as acute toxicity, influence on spontaneous and amphetamine induced locomotor activity, hypnotic activity, influence on hexobarbital narcosis and anticonvulsant activity of new analogues of pyrimidyl piperazines--ethyl 3-[4-(2-pyrimidyl)-1-piperazinyl]-3-oxopropanoate (4), 1-[4-(2-pyrimidyl)-1-piperazinyl]-1,3-butandione (5), ethyl 3-[4-(2-pyrimidyl)-1-piperazinyl]butanoate (6) and 1-[4-(2-pyrimidyl)-1-piperazinyl]-2-acetyl-1-hexanone (7)--are reported.

Amphetamine↗

The effect of activated charcoal on mouse sleep times induced by intravenously administered hypnotics.

The effect of orally administered activated charcoal (AC) on the sleep times of mice following intravenous injection of various hypnotics was investigated. Preliminary studies with phenobarbital (Pb) showed that a linear relationship exists between the Pb-induced sleep time and the logarithm of the Pb dose in both control and AC treated mice. Half-lives of Pb in the two groups were estimated to be 8.1 and 0.9 h, respectively. A linear decline in Pb-induced sleep time with increasing dose of AC was observed up to a maximum effective dose of AC beyond which dose increments caused no further reduction in sleep time. A similar relationship was observed between sleep time and the concentration of sodium sulfate in which the AC was suspended. AC treatment resulted in an 82-88 per cent reduction in sleep time induced by administration of phenobarbital, methyprylon, glutethimide, ethchlorvynol, and methaqualone. AC had no significant effect on sleep time following amobarbital or pentobarbital administration.

Administration, Oral↗