1 Effects of an imidazo-pyridine (zolpidem: 10, 20 and 30 mg) on overnight sleep and on performance the next day were studied in young adults and in middle aged individuals. The young adults were used particularly as an homogenous group to establish any possible adverse effects of the drug on sleep and on performance the next day, and the middle aged subjects with their less restful sleep were used to study efficacy. 2 In the young adults zolpidem led to a marked increase in slow wave sleep with a reduction in stage 2 sleep. There were no significant changes in REM sleep, though there was a tendency for REM sleep to be delayed. 3 In the middle aged there was a reduction in awake activity and drowsy sleep with an increase in stage 2 sleep. The latency to REM sleep was increased but the duration of REM sleep over the whole night was not reduced. 4 Digit symbol substitution and a complex reaction time task were used to study performance, but there were no residual effects with zolpidem (9 h after ingestion). 5 Zolpidem is likely to prove useful in the management of transient and short-term insomnia in healthy middle aged individuals when impaired performance the next day is to be avoided.
1Brotizolam, a triazolo-1 ,4-thienodiazepine, was studied in healthy young adults. Electroencephalographic sleep variables and subjective effects, and performance on a visuo-motor coordination task were measured. 2 In the sleep studies six males each ingested 0.2, 0.4 and 0.6 mg brotizolam overnight. All doses increased total sleep time, improved the sleep efficiency index, and reduced drowsy sleep and number of awakenings. Brotizolam 0.4 and 0.6 mg also reduced awake activity and increased stage 2 sleep. There was some evidence of a delay to the first REM period, but only 0.6 mg reduced the total duration of REM sleep. There were no changes in slow wave sleep. 3 In the performance studies six females each ingested 0.4mg in the morning and 0.2,0.4 and 0.6mg brotizolam at night. After morning ingestion of 0.4 mg there was impaired performance from 0.5 to 5.5 h. There were no residual effects after 0.2 mg brotizolam, but with 0.4 mg there was a residual effect at 9.5 h, and 0.6 mg led to impairments up to 15.0 h after ingestion. 4 Brotizolam is a short-acting hypnotic. In doses around 0.2 mg it has useful hypnotic activity free of adverse effects on sleep and residual effects on performance. With 0.4 mg the hypnotic effect is enhanced with only minimal residual effects.
1 Effects of flunitrazepam (0.25-0.50 mg) and the 1,4-triazolodiazepines, triazolam (0.25-0.50 mg) and brotizolam (0.3-0.6 mg), on day time sleep were studied by electroencephalography. 2 Flunitrazepam (0.25-0.50 mg) and triazolam (0.25-0.50 mg) reduced awake activity (P < 0.05) and improved the sleep efficiency index (P < 0.05). The higher dose of each drug increased total sleep time (P < 0.05 and < 0.01 respectively) and duration of stage 2 sleep (P < 0.01), and also delayed the first REM period (P < 0.05 and < 0.01 respectively). 3 Brotizolam (0.6 mg) markedly increased total sleep time (P <0.001) and the sleep efficiency index (P < 0.01), and prolonged stage 2 (P < 0.01) and slow wave (P < 0.01) sleep. Over the dose range 0.3-0.6 mg, the latency to stage 3 sleep was shortened (P < 0.05), and that to the first REM period lengthened (P < 0.05). 4 All three drugs improved day time sleep. However the present observations and data from previous studies suggest that flunitrazepam (0.25-0.50 mg) may be particularly appropriate for sleep at unusual times.
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