Stereoselective and non-stereoselective effects of D 600 (methoxyverapamil) in smooth muscle preparations

• Published in: European journal of pharmacology Vol. 76; no. 1; p. 67
• Main Authors: Jim, K, Harris, A, Rosenberger, L B, Triggle, D J
• Format: Journal Article
• Language: English
• Published: Netherlands 19.11.1981
• Subjects: Animals; Calcium - antagonists & inhibitors; Gallopamil - pharmacology; Guinea Pigs; Ileum - drug effects; Male; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Muscle, Smooth, Vascular - drug effects; Portal Vein - drug effects; Potassium - antagonists & inhibitors; Rats; Receptors, Adrenergic - drug effects; Stereoisomerism; Vas Deferens - drug effects; Verapamil - analogs & derivatives
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(81)90010-8

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.