Evaluation of antagonism of aconitine-induced dysrhythmias in mice as a method of detecting and assessing antidysrhythmic activity.

1 Antagonism of aconitine-induced dysrhythmias in mice as a method of detecting and assessing antidysrhythmia activity was evaluated. 2 Aconitine-induced dysrhythmias in mice appear to be selectively sensitive to antidysrhythmia agents (administered intraperitoneally) which reduce the inward sodium current in cardiac cells. 3 Antidysrhythmic agents whose mechanism of action is thought to depend on beta-adrenoceptor blockade, prolongation of cardiac monophasic action potentials or calcium antagonism are ineffective in delaying the onset of aconitine-induced dysrhythmias in mice. The inactive drugs were practolol, sotalol, bretylium, amiodarone and verapamil. 4 Comparisons of anti-dysrhythmic activities of test drugs should be based on more than one ED value and should take account of efficacy as well as potency. 5 The mouse aconitine test is a useful and rapid method of evaluating oral antidysrhythmic activity in terms of potency, efficacy and duration of action. 6 With respect to potency, efficacy, oral activity, duration of action and safety, 3 alpha-amino-5 alpha-androstan-2 beta-ol-17-one hydrochloride (Org 6001) offered the most satisfactory overall profile of the active drugs tested (Org 6001, aprindine, quinidine, disopyramide, lignocaine, mexiletine, procainamide and propranolol).