The affinity and functional effects of isoxsuprine enantiomers were investigated to determine the enantiospecificity of the β-agonistic and α-blocking effects. Functional assays on isolated smooth muscle preparations from equine common digital artery were performed to determine the apparent affinity (pD2) and intrinsic activity (α(E)) of (-)erythro-isoxsuprine (αS, βR, γR) and (+)erythro-isoxsuprine (αR, βS, γS). The affinity of two enantiomers for the different adrenoceptor types was studied by radioligand binding assays on membrane preparations from the same tissue: using (-)[3H]CGP12177 and [3H]prazosin. On noradrenaline-precontracted artery preparations (-)isoxsuprine was markedly more potent than(+)isoxsuprine in dilating preparations, indicating that the laevorotatory enantiomer has a very high apparent affinity for α-adrenoceptors. Binding studies confirmed that (-)isoxsuprine has a higher affinity than (+)isoxsuprine for α-adrenoceptors, while the (+) isomer competes for β-adrenoceptors with an affinity similar to that of propranolol. As described for other β-phenylethylamines, the two isoxsuprine enantiomers studied have different efficacies for α- and β-adrenoceptors and the effects of the commercially available mixture of stereoisomers therefore depend on the density and functional importance of the adrenoceptor types present in the tissue studied.
|Titolo:||INVESTIGATIONS ON THE STEREOSELECTIVE ACTION OF ISOXSUPRINE ON ALFA AND BETA ADRENOCEPTORS IN EQUINE COMMON DIGITAL ARTERY|
CALONI, FRANCESCA (Penultimo)
|Settore Scientifico Disciplinare:||Settore VET/07 - Farmacologia e Tossicologia Veterinaria|
|Data di pubblicazione:||1999|
|Digital Object Identifier (DOI):||10.1006/phrs.1999.0487|
|Appare nelle tipologie:||01 - Articolo su periodico|