Changes in mouse hippocampal EEG characteristics after oral administration of Ro 41-3696, nitrazepam, or zopiclone alone and in combination with ethanol

Pharmacology. 1994 Nov;49(5):278-85. doi: 10.1159/000139244.

Abstract

Ro 41-3696, a benzoquinolizinone derivative, is a partial agonist to the benzodiazepine (BDZ) receptor and is expected to be a nonsedative hypnotic. The present comparative study was performed to examine the effects of the oral administration of Ro 41-3696, nitrazepam or zopiclone alone and in combination with a 'social' dose of ethanol on mouse hippocampal EEG. Ro 41-3696 (1-10 mg/kg), nitrazepam (0.1 and 1 mg/kg), and zopiclone (1 and 10 mg/kg) each alone caused an increase in the drowsy EEG pattern associated with a decrease in the duration of hippocampal rhythmic slow-wave activity (RSA). On the other hand, nitrazepam markedly lowered, while Ro 41-3696 and zopiclone slightly lowered the RSA frequency during waking mobility. In combination with a noneffective oral dose (1 g/kg) of ethanol, the reductions in both total duration and peak frequency of RSA caused by nitrazepam, unlike those by Ro 41-3696 and zopiclone, were significantly potentiated. In addition, only nitrazepam produced motor impairment. These results suggest that Ro 41-3696 acts more selectively than nitrazepam to promote the drowsy EEG pattern, and the partial agonistic properties may minimize the residual effects during waking mobility similar to the short-acting agent zopiclone.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Azabicyclo Compounds
  • Benzodiazepines / pharmacology
  • Drug Interactions
  • Electroencephalography
  • Ethanol / pharmacology
  • Hippocampus / drug effects*
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Nitrazepam / pharmacology
  • Piperazines / pharmacology
  • Quinolizines / pharmacology*

Substances

  • Azabicyclo Compounds
  • Hypnotics and Sedatives
  • Piperazines
  • Quinolizines
  • zopiclone
  • Benzodiazepines
  • Ro 41-3696
  • Ethanol
  • Nitrazepam