In functional experiments, risperidone is selective, not for the B, but for the A subtype of alpha 1-adrenoceptors.
The potency of the antipsychotic drug, risperidone, to antagonize alpha 1A-adrenoceptor-mediated contraction in rat vas deferens and vasoconstriction in rat perfused kidney, and alpha 1B-adrenoceptor-mediated contractions in spleen from guinea-pig and mouse was evaluated and compared to that of alpha 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 1A-adrenoceptor, whereas spiperone was weakly alpha 1B-selective. Risperidone was equipotent to prazosin at alpha 1A-adrenoceptors in rat vas deferens and kidney. However, at guinea-pig and mouse splenic alpha 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 alpha 1-adrenoceptors could not be confirmed, the drug instead appears to be moderately selective (10-fold) for the A subtype.
Eltze
M
M
Department of Pharmacology, Byk Gulden, Konstanz, Germany.
D000818:Animals; D006168:Guinea Pigs; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects*
D018340:Receptors, Adrenergic, alpha-1; D018967:Risperidone; D009638:Norepinephrine; D011224:Prazosin