Antiarrhythmic and antifibrillatory properties of aprindine

Abstract

The effectiveness of aprindine, N-[3-(diethyl amino)propyl]-N-phenyl-2-indanamine, was examined against experimentally induced arrhythmias. Ouabain-induced ventricular tachycardia was reversed in six of six dogs by aprindine, 5 mg/kg i.v. The threshold for extrasytoles induced by a 250-msec train of 60 Hz 2-msec pulses starting 75 msec after the pacing pulse was elevated from a control value of 0.18 +/- mA to a peak of 0.29 +/- 0.03 mA 5 minutes after aprindine, 5 mg/kg (P less than .005). The similarly determined ventricular fibrillation threshold was increased from a control value of 2.45 +/- 0.78 mA to a maximum of 5.68 +/- 1.47 mA 30 minutes after aprindine, 5 mg/kg i.v. (P less than .025). Aprindine failed to protect against fibrillation associated with one-stage occlusion and release of the left anterior descending coronary artery. Conscious dogs 24 hours after two-stage ligation of the left anterior descending coronary artery showed ectopic beats averaging 107 +/- 5 beats/min. Aprindine, 5 mg/kg i.v., caused an initial reduction of the ectopic rate to 1 +/- 1 beats/min (P less than .001) returning to 57 +/- 19 beats/min (P less than .05) 30 minutes postdrug. An additional 5 mg/kg dose reduced the ectopic rate to 1 +/- 1 beats/min (P less than .001) returning to 15 +/- 8 beats/min (P less than .005) 60 minutes after drug. Evaluation of these animals at 48 hours showed a similar pattern, although one animal fibrillated after 5 mg/kg of aprindine. Aprindine is an effective antiarrhythmic agent in some experimental cardiac arrhythmias, but the appearance of central nervous system toxicity at therapeutic drug concentrations in conscious animals indicates that it may have a narrow margin of safety.