EVIDENCE AGAINST β‐ADRENOCEPTOR BLOCKING ACTIVITY OF DILTIAZEM, A DRUG WITH CALCIUM ANTAGONIST PROPERTIES

Abstract

In isolated spontaneously beating atria of the rat, diltiazem (0.01 to 0.1 μm) shifted the atrial rate concentration‐response curves to isoprenaline to the right in a non‐parallel manner and depressed their maxima. Under the same experimental conditions, (±)‐propranolol (0.03 to 0.1 μm) behaved as a competitive β‐adrenoceptor antagonist. Whereas (±)‐propranolol (IC50 = 12 nm) and isoprenaline (IC50 = 0.9 μm) inhibited (—)‐[3H]‐dihydroalprenolol binding to rat brain membrane preparations, diltiazem failed to do so in concentrations up to 10 μm. Diltiazem but not (±)‐propranolol, antagonized the positive chronotropic responses to calcium in spontaneously beating rat atria. It is proposed that diltiazem inhibited the tachycardia induced by isoprenaline through an effect on calcium which may be an essential modulator of the sequence of events linking the β‐adrenoceptor activation and heart rate response. 1980 British Pharmacological Society