Studies on behavioral and electroencephalographic effects of clobazam

Abstract

Behavioral and electroencephalographic effects of clobazam (CBZ), a 1, 5 benzodiazepine, were investigated in mice, rats and rabbits and compared with the effects of diazepam (DZP) and chlordiazepoxide (CDP). In EEG studies of rabbits, CBZ, DZP and CDP at doses of 2-10 mg/kg, i.v., caused a drowsy pattern, i.e., high voltage slow waves in the frontal cortex and the desynchronization of hippocampal theta wave. EEG arousal responses induced not only by auditory stimulation but also by electric stimulation of the mesencephalic reticular formation were inhibited by CBZ; CBZ was less potent than DZP, but more potent than CDP. On hypothalamic self-stimulation behavior of rats, low rate responses induced by low current brain stimulation, VI or DRL procedure were increased by oral administration of the three drugs. CBZ was less potent than DZP in the above respondings, but the same potency as CDP in VI or DRL responding and more potent in low rate responding induced by low current stimulation. The preventive effect of CBZ on MES convulsion in mice was less potent than DZP, but 2.5 times as potent as CDP. The preventive effect of CBZ was 1.3 times as potent as DZP and 2.5 times as potent as CDP. CBZ reduced the hyperemotionality of olfactory bulbectomized rats, and this effect was less than DZP in suppressing muricide. The muscle relaxant effect of CBZ in inclined screen and rotarod tests of mice was less than that of DZP. CBZ was 2.2 times as potent as CDP in potentiating thiopental sleep in mice, but less than DZP. These results indicate that CBZ is qualitatively similar to 1, 4 benzodiazepines, DZP and CDP, and is more potent than CDP, but less potent than DZP.