Effect of some beta adrenergic blocking agents and phenytoin on potentiation of quinidine antiarrhythmic activity in the mouse.
Quinidine coadministered with propranolol produces antiarrhythmic potentiation. The mechanism is uncertain although some in vitro electrophysiologic studies have suggested that it may be due to propranolol-induced cardiac beta receptor blockade. Other effects of propranolol, however, including a decrease in cardiac sympathetic nerve activity as well as some direct cardiac membrane effects might also contribute. The possible contributions of these effects were studied indirectly by coadministering quinidine with several compounds (d-propranolol, l-propranolol, d-practolol, practolol, pronethalol, and phenytoin) which have varying effects on these parameters. Antiarrhythmic activity was determined as protection against chloroform-induced ventricular arrhythmias and beta blockade as inhibition of isoproterenol-induced tachycardia. Only d- and l-propranolol and phenytoin potentiated quinidine. The d-isomer was only approximately 1/8th as potent as the l-isomer for inhibiting isoproterenol tachycardia, and the lowest dose of the d-isomer coadministered with quinidine produced antiarrhythmic potentiation but little if any inhibition of isoproterenol tachycardia. The results suggest that cardiac beta blockade alone does not adequately explain the potentiation of quinidine by propranolol in the mouse. Perhaps a decrease in cardiac sympathetic nerve activity and the direct membrane effects as occur with d-, l-, and d,l-propranolol and phenytoin may also contribute to the potentiation.
D000818:Animals; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D010672:Phenytoin / Q000494:pharmacology; D011217:Practolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy*
D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D010672:Phenytoin; D011433:Propranolol; D011802:Quinidine; D011217:Practolol