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.