Effects of oral and intravenous midazolam, triazolam and flunitrazepam on the sleep‐wakefulness cycle of rabbits.

Abstract

The effect of the new, short‐acting benzodiazepine, midazolam as well as that of triazolam and flunitrazepam on the sleep of rabbits was recorded for 6 h. Midazolam at 1 mg kg‐1 i.v. augmented both rapid eye movement sleep (REMS) and non‐REM sleep (NREMS) only in the first half of the observation period. At 10 mg kg‐1 i.v., NREMS was further increased in the first and, to a lesser degree, in the second 3‐h period, while REMS was suppressed. Both doses were less effective orally than intravenously. Qualitatively, the effect of triazolam 0.01 and 0.1 mg kg‐1 i.v. was very similar to that of the corresponding low and high intravenous doses of midazolam, except that the high dose of triazolam had a prolonged effect on total sleep time. Like midazolam, triazolam was substantially less effective orally than intravenously. Flunitrazepam at 0.1 and 1 mg kg‐1 i.v. produced almost the same effects as midazolam and triazolam at the respective low and high intravenous doses, but had a longer duration of action. In contrast to midazolam and triazolam, flunitrazepam was almost as active orally as intravenously. 1983 The British Pharmacological Society