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The electroencephalographic (EEG) effects of 7-chloro-5-(o-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1, 4-benzodiazepine-2-thione (Sch 161, quazepam) were investigated in unanesthetized rats and rabbits with chronic electrode implants, and the effects were compared with those of flurazepam and diazepam. In freely moving rats, quazepam at doses of 10 to 30 mg/kg, p.o., induced an increase in drowsy EEG pattern periods: high amplitude slow waves and spindle bursts in the cortical EEG and desynchronization of the hippocampal theta waves. Quazepam at doses of 10 to 30 mg/kg significantly decreased the onset of the drowsy EEG pattern after p.o. administration of rats in a dose-dependent manner, while flurazepam and diazepam reduced it only at higher doses of 20 to 30 mg/kg, p.o. In rabbits, quazepam at doses of 0.5 to 5 mg/kg, i.v., evoked a drowsy EEG pattern similar to that of flurazepam (1 to 5 mg/kg) or diazepam (1 to 2 mg/kg). Quazepam at higher doses caused sedation and a slight muscle relaxation in both rats and rabbits, which were weaker than those of flurazepam or diazepam. In both rats and rabbits, quazepam and flurazepam depressed the EEG arousal response to auditory stimulation but not to electrical stimulation of the midbrain reticular formation or the posterior hypothalamus, while the arousal response to either auditory or brain stimulation was markedly suppressed by diazepam. The recruiting response was not altered by quazepam, flurazepam and diazepam. Quazepam has no effect on the photic driving response to flash light in the occipital cortex of the rabbit, while the response was suppressed moderately by flurazepam and markedly suppressed by diazepam. Quazepam (2 mg/kg) suppressed either the hippocampal or amygdaloid afterdischarges. These results suggest that the EEG effect of quazepam is different to those of flurazepam and diazepam in qualitative aspects and that quazepam is likely to be an effective sleep-promoting drug with slight adverse reactions.

Electroencephalographic study with Sch 161 (quazepam), a new benzodiazepine hypnotic, in rats and rabbits.