title: Diltiazem: lack of myocardial beta-adrenergic receptor-binding capacity.
abstract: It has been suggested that the mechanism of action of the calcium blocker diltiazem (DZ) is via beta-receptor blockade. In order to test this hypothesis, the effects of DZ on the competitive binding of 3H-dihydroalprenolol (3H-DHA) to myocardial beta-receptors were evaluated and compared to those of a known beta-receptor agonist. Preliminary validation studies indicate that binding sites for 3H-DHA exhibit stereospecificity for isoproterenol (IP) (l-IP>d-IP) and show greater affinity for l-epinephrine compared to l-norepinephrine. In order to test the binding capacity of DZ to beta-adrenergic receptors, binding-concentration relationships were constructed for 3H-DHA (3--60 nM) in the presence of no drugs, l-IP (10(-4) M), or DZ (2.2 x 10(-6) M). 3H-DHA binding was significantly inhibited over the entire concentration range by 1-IP but was unaffected by the other conditions. This study was repeated using two different concentrations of DZ (2.2 x 10(-5) and 2.2 x 10(-7) M) with a similar lack of inhibition of 3H-DHA binding. These data indicate that DZ does not bind to myocardial beta-receptors and, therefore, does not appear to act via a beta-receptor-blocking activity.
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive; D001679:Biogenic Amines / Q000494:pharmacology; D004082:Dihydroalprenolol; D004110:Diltiazem / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D001679:Biogenic Amines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D004110:Diltiazem