Triazolam and platelet-aggregating factor.
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Biomedical subjects
Publications and source records attributed to I Oswald.
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The effects of hypnotics on descriptive and functional aspects of electrophysiological sleep parameters are assessed in this report. Because of the arbitrary definition of some of the criteria underlying the conventional sleep stage scoring procedure, computer-aided methods of EEG analysis have become increasingly important for recording and interpreting pharmacological effects on sleep. Of particular interest are the changes of EEG slow-wave activity, since this parameter varies as a function of prior sleep and waking. Several types of interaction between hypnotics and sleep regulation are discussed, some recent pharmacological developments are highlighted, and some common problems in clinical trials are specified.
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Nine subjects who believed themselves to be poor sleepers, of mean age 58 years, took a placebo for 7 days, then ritanserin 5 mg for 20 days, followed by 3 days on placebo. Sleep was recorded electrophysiologically on 2 nights during baseline, 2 early drug nights, 2 late drug nights and the 2nd and 3rd withdrawal nights. Ratings of sleep quality were collected each morning. Ritanserin, a 5HT2 antagonist, caused a persistent doubling of the amount of EEG slow wave sleep, without altering the total duration of sleep. Ritanserin decreased the frequencies of awakening and after about a week it appeared to improve the subjective quality of sleep. Sleep was then impaired during withdrawal, as indicated by decreased duration and poorer subjective quality, being worst on the 3rd withdrawal night.
To test further the conclusions of preliminary reports that regular use of a rapidly-eliminated hypnotic might cause daytime anxiety, 82 women and 38 men, mean age 53, who claimed to be poor sleepers, took a capsule nightly for 45 nights. On 25 consecutive nights the capsule contained triazolam 0.5 mg (40 subjects), lormetazepam 2 mg (40 subjects) or continued placebo (40 subjects). Both drugs improved sleep, but compared with placebo or lormetazepam-takers, triazolam-takers became more anxious on self-ratings, were judged more often to have had a bad response by an observer, more often wrote down complaints of distress, and suffered weight loss. After about 10 days of regular triazolam they tended to develop panics and depression, felt unreal, and sometimes paranoid. The very short life of triazolam, leading to daytime withdrawal symptoms, may account for some of the observations, but enhancement of benzodiazepine inverse agonist activity is also hypothesized.
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Twelve men with severe and long-standing atopic eczema were admitted to a double-blind trial to establish the effects of trimeprazine tartrate, trimipramine maleate, and placebo on nocturnal scratching. Neither of the drugs altered the likelihood of a scratching bout beginning in wakefulness or in any stage of sleep. However, both drugs, especially trimipramine, made sleep less broken, and the reduced time spent in stage 1 of sleep accounted for a modest reduction in the overall amount of scratching during the night.