Inhibition of aconitine-induced mortality in the conscious rat: a screening test for antiarrhythmic drugs.

A test for inhibition of mortality induced by intravenous injection of aconitine in rats is proposed as a particularly valid method, owing to its simplicity and degree of specificity, for inclusion among the preliminary screening tests for antiarrhythmic activity. LD50 (63.5 micrograms/kg, i.v.) and LD99 (118.9 micrograms/kg, i.v.) values of aconitine were determined. The dose employed for screening was 100 micrograms/kg i.v., which in control animals produced a death rate of 97.7% (293 deaths/300 treated animals). The protection produced by various drugs belonging to different groups of antiarrhythmics was studied. ED50s, expressed in mg/kg i.p., were as follows: Class I antiarrhythmics: flecainide, 5.5; E-4017, 30.0; lorcainide, 30.9; quinidine, 41.1; diphenylhydantoin, 42.3; lidocaine, 48.5; ajmaline: 53.9; procainamide, 61.3. Class II antiarrhythmics: pindolol 22.8; propranolol, 24.9; oxprenolol, 38.0; labetalol, 60.7; atenolol, 100.0; metoprolol, approximately 160; acebutalol, greater than 160; timolol, greater than 160. Class III antiarrhythmics: amiodarone, greater than 160. Class IV antiarrhythmics: verapamil, diltiazem and nifedipine were inactive up to 40 mg/kg. The test would appear to be selective for membrane-stabilizing agents (class I) and beta-blockers (class II), but in view of the magnitudes of activity found, it should be used in combination with other antiarrhythmic tests.