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 investigated to determine the enantiospecificity of the beta-agonistic and alpha-blocking effects. Functional assays on isolated smooth muscle preparations from equine common digital artery were performed to determine the apparent affinity (pD(2)) and intrinsic activity (alpha(E)) of (-)erythro-isoxsuprine (alphaS, betaR, gammaR) and (+)erythro-isoxsuprine (alphaR, betaS, gammaS). The affinity of two enantiomers for the different adrenoceptor types was studied by radioligand binding assays on membrane preparations from the same tissue, using (-)[(3)H]CGP12177 and [(3)H]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 alpha-adrenoceptors. Binding studies confirmed that (-)isoxsuprine has a higher affinity than (+)isoxsuprine for alpha-adrenoceptors, while the (+) isomer competes for beta-adrenoceptors with an affinity similar to that of propranolol. As described for other beta-phenylethylamines, the two isoxsuprine enantiomers studied have different efficacies for alpha- and beta-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.
Belloli
C
C
Department of Animal Health and Welfare, Division of Veterinary Pharmacology and Toxicology, University of Bari, Tecnopolis CSATA, Novus Ortus, Strada Provinciale per Casamassima Km.3, Bari, Valenzano, 70010, Italy.
Badino
P
P
Carcano
R
R
Odore
R
R
Arioli
F
F
Caloni
F
F
Re
G
G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001667:Binding, Competitive; D005260:Female; D005552:Forelimb; D006736:Horses; D066298:In Vitro Techniques; D007556:Isoxsuprine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D014034:Toes / Q000098:blood supply*; D014316:Tritium; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D007556:Isoxsuprine; C033394:CGP 12177; D009638:Norepinephrine; D011224:Prazosin