Abstract
Electroencephalographic (EEG) effects of 450191-S and its metabolites were investigated in unanesthetized rabbits with chronic electrode implants, and they were compared with those of nitrazepam and estazolam. 450191-S at doses of 0.1 ?? 0.5 mg/kg, i.v., induced a drowsy pattern of spontaneous EEG: high voltage slow waves and spindle bursts increased in the cortex and amygdala, while the hippocampal theta rhythm was desynchronized. In addition, low voltage fast waves appeared particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus was markedly suppressed by 450191-S. The photic driving response elicited by a flash light in the visual cortex was significantly suppressed by 450191-S. 450191-S showed no significant effect on the recruiting response. The EEG effects of nitrazepam were qualitatively similar but less potent and shorter in duration of action than those of 450191-S. The effects of estazolam were approximately as potent as those of 450191-S, but its duration of action was much shorter than that of 450191-S. 450191-S was more potent than nitrazepam and approximately equipotent to estazolam in suppressing hippocampal and amygdaloid after-discharges. The EEG effects of M-1 and M-2 were similar to those of 450191-S in both qualitative and quantitative aspects. The effects of M-A were quantitatively similar but less potent and shorter in duration of action than those of 450191-S.
