Evidence against beta-adrenoceptor blocking activity of diltiazem, a drug with calcium antagonist properties.
1 The isolated spontaneously beating atria of the rat, diltiazem (0.01 to 0.1 microM) 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 microM) behaved as a competitive beta-adrenoceptor antagonist. 2 Whereas (+/-)-propranolol (IC50 = 12 nM) and isoprenaline (IC50 = 0.9 microM) inhibited (-)-[3H]-dihydroalprenolol binding to rat brain membrane preparations, diltiazem failed to do so in concentrations up to 10 microM. 3 Diltiazem but not (+/-)-propranolol, antagonized the positive chronotropic responses to calcium in spontaneously beating rat atria. 4 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 beta-adrenoceptor activation and heart rate response.
D000319:Adrenergic beta-Antagonists; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors; D004082:Dihydroalprenolol / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D004082:Dihydroalprenolol; D011433:Propranolol; D004110:Diltiazem; D007545:Isoproterenol; D002118:Calcium