Effect of N-desmethyldiazepam (nordiazepam) and a precursor, potassium clorazepate, on sleep in man

Abstract

1 The effect of N-desmethyldiazepam (nordiazepam, 5 and 10 mg) and potassium clorazepate (15 mg, a precursor of nordiazepam) on sleep was studied in six healthy adult males. Electroencephalography (EEG) was used for sleep measures, and analogue scales were used for subjective assessments of well-being and sleep quality. 2 Effects on total sleep time were limited to the night of ingestion. There were increases with nordiazepam (5 and 10 mg) (P = 0.05) and 0.001 respectively), and with clorazepate (15 mg) (P = 0.01). Sleep onset latencies were shortened, particularly with nordiazepam, and awakening to stage 0 activity was reduced, by both drugs. The latency to stage 3 was reduced by nordiazepam (5 and 10 mg) (P = 0.05). 3 There were no effects of nordiazepam (5 mg) on the duration (min) of sleep stages. Nordiazepam (10 mg) and clorazepate (15 mg) reduced the duration of stage 0 and stage 1, and there were increases in stage 2. Reduced stage 1 and increased stage 2 sleep were observed during the recovery night. No effects were observed with stage 3, but there was evidence that stage 4 activity was depressed on the recovery night only. No effects were observed on REM sleep, except that the appearnace of the first REM period was delayed with clorazepate (15 mg) P = 0.01). The effect of nordiazepam (10 mg) and clorazepate (15 mg) were comparable, and each modified sleep for about 28-30 h after ingestion. 4 With nordiazepam (10 mg) and clorazepate (15 mg) the subjects, as a group, reported improved sleep, but subjective assessments of well-being were not altered. Correlations were calculated for sleep measures and subjective assessments.