Circadian susceptibility rhythm to neuroleptics: tetrabenazine

In order to clarify the influences of situational factors on the effects of psychotropic drugs, the sedative effects of tetrabenazine after injection at various times of the day were studied. When 50 mg/kg body weight of tetrabenazine was injected into rats at eight different times of the day (07:30-19:30 dark, 19:30-07:30 light), a circadian rhythm of sedative effect was observed with a peak sedative time of 1490 min at 10:30 and a nadir of 736 min at 07:30. With 10 mg/kg body weight of tetrabenazine a similar circadian rhythm of sedative effect was observed. This rhythm did not appear to be due to differences of metabolism of tetrabenazine in the tissues, but rather to be closely related to daily fluctuation of serotonin synthesis and release in the brain.