INVESTIGATIONS ON THE STEREOSELECTIVE ACTION OF ISOXSUPRINE ON α- AND β-ADRENOCEPTORS IN EQUINE COMMON DIGITAL ARTERY

• Published in: Pharmacological research 1999-08, Vol.40 (2), p.177-182
• Main Authors: BELLOLI, CHIARA, BADINO, PAOLA, CARCANO, ROBERTA, ODORE, ROSANGELA, ARIOLI, FRANCESCO, CALONI, FRANCESCA, RE, GIOVANNI
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic beta-Agonists - metabolism; Adrenergic beta-Agonists - pharmacology; Animals; Arteries - drug effects; Arteries - metabolism; Arteries - physiology; Binding, Competitive; Female; Forelimb; Horses; In Vitro Techniques; Isoxsuprine - chemistry; Isoxsuprine - metabolism; Isoxsuprine - pharmacology; isoxsuprine, equine common digital artery, α- and β-adrenoceptors, drug chirality; Male; Membranes - drug effects; Membranes - metabolism; Norepinephrine - pharmacology; Prazosin - metabolism; Propanolamines - metabolism; Radioligand Assay; Receptors, Adrenergic, alpha - drug effects; Receptors, Adrenergic, alpha - metabolism; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - metabolism; Stereoisomerism; Toes - blood supply; Tritium; Vasoconstriction - drug effects
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1999.0487

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 (αE) 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. 1999 Academic Press@p$hr