In functional experiments, risperidone is selective, not for the B, but for the A subtype of α1-adrenoceptors

Abstract

The potency of the antipsychotic drug, risperidone, to antagonize α 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and α 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of α 1-adrenoceptor subtype-discriminating antagonists. Prazosin was found to be unselective; 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), 5-methyl-urapidil, indoramin and (+)-niguldipine were confirmed as selective for the α 1A-adrenoceptor, whereas spiperone was weakly α 1B-selective. Risperidone was equipotent to prazosin at α 1A-adrenoceptors in rat vas deferens and kidney. However, at guinea-pig and mouse splenic α 1B-adrenoceptors, the affinity values of risperidone were 10-fold lower than those of prazosin. Thus, in functional experiments the presumed high selectivity of risperidone for the B subtype of α 1-adrenoceptors could not be confirmed, the drug instead appears to be moderately selective (10-fold) for the A subtype.