ATYPICALITY OF SEVERAL ANTIPSYCHOTICS ON THE BASIS OF IN-VIVO DOPAMINE-D-2 AND SEROTONIN-5HT(2) RECEPTOR OCCUPANCY

An in vivo receptor binding technique was used to evaluate the binding profiles of typical and atypical antipsychotic drugs to striatal dopa mine-D-2 and frontal serotonin-5-HT2 receptors in a rat brain using mo re specific ligands than those previously employed. [H-3]-YM-09151-2 o r [H-3]-ketanserin was injected into the tail vein 10 minutes after ad ministration of test drugs. One hour after the ligand injection, radio activities in the striatum, frontal cortex, and cerebellum were counte d to obtain receptor occupancies by the test drugs. Higher ratios of p otency in occupying 5-HT2 versus D-2 receptors were found for clozapin e, RMI-81512, and tiospirone compared to haloperiodol and pimozide. Zo tepine, mosapramine, and clocapramine produced ratios that fall betwee n these two groups. Chlorpromazine was exceptional as a typical antisp ychotic by these criteria. Relatively strong antagonism of 5-HT2 recep tors by atypical antipsychotics was confirmed by this in vivo measure of receptor binding using more selective ligands than those used in pr evious studies.