TIME-COURSE OF DOPAMINE-D(2) AND SEROTONIN-5-HT(2) RECEPTOR OCCUPANCYRATES BY HALOPERIDOL AND CLOZAPINE INVIVO

In vivo occupancy of dopamine-D1, D2 and serotonin-5-HT2 receptors by haloperidol 10 mg/kg and clozapine 20 mg/kg were studied. Rats were in jected intravenously with [H-3]-YM-09151-2, [H-3]-SCH23390, or [H-3]-k etanserin 10 min after the administration of the tested drugs. Fifteen to 240 min after the ligand injection, the receptor occupancy rates o f the drugs in the striatum and frontal cortex were calculated. Clozap ine demonstrated the higher 5-HT2 and lower D2 occupancies in the resp ective regions. A dose-response analysis of D2 and 5-HT2 receptor occu pancy by the drugs consolidated the higher 5-HT2 binding affinity of c lozapine in comparison with haloperidol. The present methodology may s erve as an accurate tool to evaluate the peculiarity of various antips ychotics.