CHARACTERIZATION OF TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS BASED ONIN-VIVO OCCUPANCY OF SEROTONIN-2 AND DOPAMINE-2 RECEPTORS

Atypical antipsychotic drugs related to clozapine may be distinguishab le from typical antipsychotic drugs by having a greater potency in vit ro at serotonin2 (5-HT2) receptors relative to dopamine2 (D2) receptor s. The in vivo potencies of 10 typical and 10 putative atypical antips ychotic drugs in occupying D2 and 5-HT2 receptors in rat brain are rep orted here. There is no significant difference in the average potency of the two groups of antipsychotic drugs in preventing the in vivo bin ding of N-[H-3] methylspiperone to 5-HT2 receptors in the cortex. Howe ver, the average potency of the atypical antipsychotic drugs is about 8-fold less than typical antipsychotic drugs in preventing N-[H-3] met hylspiperone binding to D2 receptors in the striatum. Thus, all of the atypical antipsychotic drugs that are clozapine-like have a greater r elative affinity in vivo for the 5-HT2 than the D2 receptor. As a grou p, the typical antipsychotic drugs tend to be equipotent at both recep tors. The average relative potency of the group of typical antipsychot ic drugs at 5-HT2 vs. D2 receptors is essentially equal when examined in vivo vs. in vitro. Atypical antipsychotic drugs are slightly but si gnificantly more potent in vivo at D2 receptors in the olfactory tuber cle than the striatum. For only the typical antipsychotic drugs, the i n vivo and in vitro potencies in occupying D2 receptors are correlated with their average clinical dosage. Thus, the relative in vivo potenc y of clozapine-related drugs at 5-HT2 vs. D2 receptors may help identi fy these compounds as atypical antipsychotic drugs.