Investigations on the stereoselective action of isoxsuprine on alpha- and beta-adrenoceptors in equine common digital artery

The affinity and functional effects of isoxsuprine enantiomers were investi gated to determine the enantiospecificity of the beta-agonistic and alpha-b locking effects. Functional assays on isolated smooth muscle preparations f rom equine common digital artery were performed to determine the apparent a ffinity (pD(2)) and intrinsic activity (alpha(E)) of(-)erythroisoxsuprine ( alpha S, beta R, gamma R) and (+)erythro-isoxsuprine (alpha R, beta S, gamm a S). The affinity of two enantiomers for the different adrenoceptor types was studied by radioligand binding assays on membrane preparations from the same tissue, using (-)[H-3]CGP12177 and [H-3]prazosin. On noradrenaline-pr econtracted artery preparations (-)isoxsuprine was markedly more potent tha n(+)isoxsuprine in dilating preparations, indicating that the laevorotatory enantiomer has a very high apparent affinity for alpha-adrenoceptors. Bind ing studies confirmed that(-)isoxsuprine has a higher affinity than (+)isox suprine for alpha-adrenoceptors, while the (+) isomer competes for beta-adr enoceptors with an affinity similar to that of propranolol. As described fo r other beta-phenylethylamines, the two isoxsuprine enantiomers studied hav e different efficacies for alpha- and beta-adrenoceptors and the effects of the commercially available mixture of stereoisomers therefore depend on th e density and functional importance of the adrenoceptor types present in th e tissue studied. (C) 1999 Academic Press.