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 α-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 α-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.