Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy.

An in vivo receptor binding technique was used to evaluate the binding profiles of typical and atypical antipsychotic drugs to striatal dopamine-D2 and frontal serotonin-5-HT2 receptors in a rat brain using more specific ligands than those previously employed. [3H]-YM-09151-2 or [3H]-ketanserin was injected into the tail vein 10 minutes after administration of test drugs. One hour after the ligand injection, radioactivities in the striatum, frontal cortex, and cerebellum were counted to obtain receptor occupancies by the test drugs. Higher ratios of potency in occupying 5-HT2 versus D2 receptors were found for clozapine, RMI-81512, and tiospirone compared to haloperiodol and pimozide. Zotepine, mosapramine, and clocapramine produced ratios that fall between these two groups. Chlorpromazine was exceptional as a typical antispychotic by these criteria. Relatively strong antagonism of 5-HT2 receptors by atypical antipsychotics was confirmed by this in vivo measure of receptor binding using more selective ligands than those used in previous studies.