Immediate and residual effects in man of the metabolites of diazepam

Abstract

1 Immediate and residual effects of diazepam and its metabolites on visuomotor co-ordination have been studied in man. Performance was observed from 10.0-16.0 h after overnight ingestion of diazepam (5 and 10 mg), temazepam (10, 20 and 30 mg), oxazepam (15, 30 and 45 mg) and nordiazepam (5 and 10 mg), and from 0.5-6.5 h after morning ingestion of diazepam (10 mg), temazepam (20 mg), oxazepam (30 mg), and nordiazepam (5 and 10 mg). Immediate and residual effects of diazepam and temazepam were also studied on a choice response time test.

2 Visuo-motor co-ordination was not impaired after the overnight ingestion of 5 and 10 mg diazepam, 10, 20 and 30 mg temazepam, 15 and 30 mg oxazepam and 5 and 10 mg nordiazepam, though there was a trend of impaired performance over the dose range used with temazepam 10.0 h after ingestion. With 45 mg oxazepam performance at 10.0 h was impaired compared with performance at 14.0 (P < 0.01) and 16.0 h (P < 0.001). Performance on the choice response time test was not impaired after the overnight ingestion of 5 and 10 mg diazepam and 10, 20 and 30 mg temazepam.

3 With morning ingestion visuo-motor co-ordination was impaired at 0.5 (P < 0.01) and 2.5 h (P < 0.05) after 10 mg diazepam, at 0.5 (P < 0.001) after 20 mg temazepam, and at 2.5 (P < 0.01) and 4.5 h (P < 0.05) after 30 mg oxazepam. Performance 6.5 h after 10 mg nordiazepam was impaired compared with performance 0.5 and 2.5 h (P < 0.01) after ingestion. Performance on the choice response time test was impaired 1.0 h after ingestion of 10 mg diazepam (P < 0.01) and 20 mg temazepam (P < 0.05).

4 It is considered that diazepam (5-10 mg), temazepam (10-20 mg) and oxazepam (15-30 mg) would be useful hypnotics within the dose ranges indicated, at least for occasional use, when impaired performance the next day would be unacceptable. The studies with nordiazepam suggest that, though this drug may have limited effects on performance, it may have persistent effects on behaviour consistent with its clinical use as an anxiolytic.