Activity of the hypnotics, flunitrazepam and triazolam, in man.

Abstract

1 Effects of flunitrazepam and triazolam (0.25 and 0.5 mg) on sleep and on performance were studied in six healthy adult males. Sleep was assessed by electroencephalography and analogue scales, and performance by a visuo-motor coordination task. 2 Over the same dose range triazolam had a more pronounced effect than flunitrazepam. Total sleep time was increased by 0.25 and 0.5 mg triazolam, and by 0.5 mg flunitrazepam. Both drugs decreased awake activity and drowsy sleep, though the effect of flunitrazepam was limited to the 0.5 mg dose and restricted to the first 6 h after sleep onset. There were no changes in slow wave sleep. 3 Latency to the first period of rapid eye movement (REM) sleep was increased with 0.5 mg triazolam, and when doses were combined (0.25-0.5 mg) the latencies with both drugs were increased. Both doses of triazolam reduced the duration and percentage of REM sleep during the early part of the night, though the whole night duration of REM sleep was not changed. 4 After the morning ingestion of 0.25 mg flunitrazepam performance was impaired for 2.0 h, but there were no residual effects when 0.25 or 0.5 mg were taken at night. With the morning ingestion of 0.25 mg triazolam performance was impaired from 0.5 to at least 5.0 h after ingestion. There were no residual effects with 0.25 mg overnight, but with 0.5 mg triazolam there was an effect on performance 10 h after ingestion with recovery within 1.5 h (11.5 h of ingestion). 5 Triazolam (0.25 mg) and 0.5 mg flunitrazepam provide useful hypnotic activity when impaired performance the next day is to be avoided. The activity of 0.5 mg triazolam is accompanied by only limited residual sequelae compared with some other benzodiazepines of comparable efficacy, and so may prove to be useful when a more powerful effect is required.

Daytime wakefulness following a bedtime oral dose of zolpidem 20 mg, flunitrazepam 2 mg and placebo.

“…Assessment of et al, 1982;Nicholson & Stone, 1980). Howdaytime sleepiness is therefore a major concern ever, both short and long-acting benzodiazepines in evaluating hypnotic treatment. have, in addition to their hypnotic activity, other The benzodiazepines, which are most widely pharmacological effects such as anterograde used as hypnotics, have a range of elimination amnesia, myorelaxing or anxiolytic/disinhibiting half-lives, from short (few hours) to medium effects that may give rise to side-effects.…”

Approaches in the evaluation of hypnotics: studies with triazolam.

“…To address these questions, triazolam 0.25 and 0.5 mg was compared with flurazepam 15 and 30 mg, secobarbital 100 mg and flunitrazepam 0.25 and 0.5 mg in their effects on performance and cognitive ability. The overall results of performance studies (Roth, Kramer & Lutz, 1977;Nicholson & Stone, 1980) showed that all the compounds improved sleep efficiency, although placebo produced the worst sleep efficiency. A dose-response relationship for triazolam, flurazepam and flunitrazepam was observed with the higher dose of both hypnotics showing better sleep efficiency on all measures than the corresponding lower dose of the three compounds.…”

Effects of Triazolam (0.5 mg) on Sleep, Performance, Memory, and Arousal Threshold

“…In sleep laboratory studies, triazolam (Halcion), a triazolobenzodiazepine, has been demonstrated to be an effective hypnotic in doses ranging from 0.25-1.0 mg. [1][2][3][4][5][6][7][8][9] In addition, results of outpatient studies and other investigations which used self-report measures to evaluate hypnotic efficacy have shown that sleep is subjectively improved after triazolam administration1 0 '- 1 8 Pharmacokinetic measures indicate that both triazolam and its active metabolite, 7-a-hydroxy triazolam, have short half-lives, reported to be within the range of 2.1-lo hours. 19 -2 1 The relatively rapid metabolism and clearance of triazolam suggest that, at least at lower doses within the effective range, this benzodiazepine may promote improved sleep without producing a drug-induced performance impairment the following morning.…”