Stereoselective and non-stereoselective effects of D 600 (methoxyverapamil) in smooth muscle preparations.
Mechanical responses in guinea-pig ileal longitudinal, rat vasa deferentia and rat portal vein smooth muscle strips elicited by receptor activation (muscarinic or alpha-adrenergic) or by K+ depolarization were blocked by D 600 (methoxyverapamil). Stereoselectivity was observed with the (-)-enantiomer being more potent than the (+)-enantiomer (the ratio varying from 6 to 180). The tonic (slow) component of response was more sensitive than the phasic (fast) component. D 600 competitively blocked binding of (-)-[3H]QNB and [3H]WB 4101 to muscarinic and alpha-adrenergic receptors respectively, but in marked contrast to the effects on mechanical responses antagonism of ligand binding was non-stereoselective. It is suggested that stereoselectivity of action of D 600 may be a useful criterion to distinguish between its several sites of action.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D005711:Gallopamil / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects; D011188:Potassium / Q000037:antagonists & inhibitors*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects; D014700:Verapamil / Q000031:analogs & derivatives*
D011941:Receptors, Adrenergic; D005711:Gallopamil; D014700:Verapamil; D011188:Potassium; D002118:Calcium