Mechanism of action of quinidine on heart rate in the dog.
The known vagolytic effect of quinidine has been termed "atropine-like." This effect was studied in vitro and in vivo. Unlike atropine, quinidine was not found to exert any competitive antagonism to acetylcholine at the muscarine-sensitive cholinoceptors of isolated guinea-pig atria. In the narcosed dog subjected to vagal stimulation, the effects of slow perfusion of quinidine (0.5 mg/kg/min for 120 min) were also different in several ways from those of atropine. The tachycardia induced by quinidine was not concomitant with an inhibition of the cardiomoderation caused by vagal stimulation. Tachycardia appeared at low plasma levels, whereas reduction of vagal influence only occurred at high concentrations. Even then, the effects of vagal stimulation were never totally suppressed. After propranolol, quinidine had no tachycardiac action. This could not be attributed to any difference in metabolism because plasma levels of quinidine were the same in dogs pretreated or not with propranolol. Evidence reported here suggests that the cardioacceleration induced by quinidine is not due to a direct vagolytic action. The slight lowering of vascular resistance and arterial pressure observed cannot fully account for this effect either. An adrenergic mechanism involving beta receptors seems likely. In any case, to describe the effects of quinidine on heart rate as atropine-like is evidently inappropriate and misleading.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D011433:Propranolol; D011802:Quinidine; D000109:Acetylcholine