Changes in mouse hippocampal EEG characteristics after oral administration of Ro 41-3696, nitrazepam, or zopiclone alone and in combination with ethanol.
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.
Tsuboi
M
M
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Tanaka
Y
Y
Himori
N
N
D000818:Animals; D053961:Azabicyclo Compounds; D001569:Benzodiazepines / Q000494:pharmacology; D004347:Drug Interactions; D004569:Electroencephalography; D000431:Ethanol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009567:Nitrazepam / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology*
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011807:Quinolizines; C515050:zopiclone; D001569:Benzodiazepines; C092091:Ro 41-3696; D000431:Ethanol; D009567:Nitrazepam