It has been suggested that the mechanism of action of the calcium blocker diltiazem (DZ) is via β-receptor blockade. In order to test this hypothesis, the effects of DZ on the competitive binding of 3H-dihydroalprenolol (3H-DHA) to myocardial β-receptors were evaluated and compared to those of a known β-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 β-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 l-IP but was unaffected by the other conditions. This study was repeated using 2 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 β-receptors and, therefore, does not appear to act via a β-receptor-blocking activity.
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