COMPARISON OF BINDING OF H-3 DESMETHOXYVERAPAMIL AND H-3 MIBEFRADIL IN VASCULAR SMOOTH-MUSCLE AND HEART MEMBRANES - POSSIBLE BINDING OF MIBEFRADIL TO A SITE DISTINCT FROM THE PHENYLALKYLAMINE-BINDING SITE

Binding of H-3-mibefradil (Re-40-5967 CAS 116666-63-8) and H-3-desmeth oxyverapamil (GAS 67018-79-5) to membranes of vascular smooth muscle c ells (VSMC) and heart was studied. Direct binding studies in VSM demon strated the presence of significantly higher amounts of binding sites for mibefradil as compared to those for verampamil. In competition exp eriments both unlabelled drugs displaced 3H-desmethoxyverapamil with t he same affinity. In contrast, binding of H-3-mibefradil was 30-fold m ore potently displaced by mibefradil than verapamil. It was concluded that mibefradil binds to a site distinct from the verapamil site on th e calcium channel. This site could be allosterically linked to the phe nylalkylamine site.