In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha sub(1)-adrenoceptors

The potency of the antipsychotic drug, risperidone, to antagonize alpha sub(1A)-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha sub(1B)-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha sub(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 alpha sub(1A)-adrenoceptor, whereas spiperone was weakly alpha sub(1B)-selective. Risperidone was equipotent to prazosin at alpha sub(1A)-adrenoceptors in rat vas deferens and kidney. However, at guinea-pig and mouse splenic alpha sub(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 a sub(1)-adrenoceptors could not be confirmed, the drug instead appears to be moderately selective (10-fold) for the A subtype.