Imidazobenzodiazepines: sleep and performance studies in humans.

For hypnotics in which a fast elimination phase dominates the plasma decay, the initial fall in concentration from the peak value may nevertheless be slower than that of compounds with a sustained and rapid distribution. Drugs with fast elimination may therefore improve sleep throughout the rest period, even though residual sequelae, if any, around awakening will disappear rapidly. In the context of the balance between efficacy and residual effects, the activity of two imidazobenzodiazepines, loprazolam (0.5, 1.0, and 1.5 mg) and midazolam (10, 20, and 30 mg), each with fast elimination (about 6 and 2 hours, respectively) has been studied in healthy men with sleep electroencephalography, measures of performance, and assessments of mood. Loprazolam may be appropriate when a sustained hypnotic effect is required and when some residual activity is acceptable, while midazolam is likely to be suitable for those involved in skilled activity and may be useful in the management of sleep disturbance associated with shift work.