Comparison of binding of 3H-desmethoxyverapamil and 3H-mibefradil in vascular smooth muscle and heart membranes. Possible binding of mibefradil to a site distinct from the phenylalkylamine-binding site.
Binding of 3H-mibefradil (Ro-40-5967, CAS 116666-63-8) and 3H-desmethoxyverapamil (CAS 67018-79-5) to membranes of vascular smooth muscle cells (VSMC) and heart was studied. Direct binding studies in VSM demonstrated the presence of significantly higher amounts of binding sites for mibefradil as compared to those for verampamil. In competition experiments both unlabelled drugs displaced 3H-desmethoxyverapamil with the same affinity. In contrast, binding of 3H-mibefradil was 30-fold more potently displaced by mibefradil than verapamil. It was concluded that mibefradil binds to a site distinct from the verapamil site on the calcium channel. This site could be allosterically linked to the phenylalkylamine site.
Ratner
E I
EI
Institute of Experimental Cardiology, Cardiology Research Center, Moscow (Russia).
Bochkov
V N
VN
Tkachuk
V A
VA
D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002417:Cattle; D006801:Humans; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D020748:Mibefradil; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics*; D014700:Verapamil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; C043184:4-desmethoxyverapamil; D014700:Verapamil