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

Br J Clin Pharmacol. 1983;16 Suppl 1(Suppl 1):29S-35S. doi: 10.1111/j.1365-2125.1983.tb02268.x.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Benzodiazepines / pharmacology*
  • Electroencephalography
  • Electromyography
  • Flunitrazepam / pharmacology*
  • Injections, Intravenous
  • Male
  • Midazolam
  • Rabbits
  • Sleep / drug effects*
  • Sleep, REM / drug effects
  • Triazolam / pharmacology*
  • Wakefulness / drug effects*

Substances

  • Anti-Anxiety Agents
  • Benzodiazepines
  • Triazolam
  • Flunitrazepam
  • Midazolam