Effect of SC‐40230, a new class I antiarrhythmic agent, on canine ventricular tachycardias

SC‐40230, α‐[2‐[acetyl(1‐methylethyl)amino]ethyl]‐α‐(2‐chlorophenyl)‐1‐piperidinebutanamide, a new class I antiarrhythmic agent, was tested for efficacy against coronary ligation‐induced arrhythmias and ouabain toxicity arrhythmias in dogs. Doses of 9mg/kg i.v. and 15, 25, and 35 mg/kg p.o. significantly reduced ectopic rate in conscious dogs that had undergone ligation of the left anterior descending coronary artery 24 hr prior to testing. Plasma concentrations of SC‐40230 ranging from 3 to 9 μg/ml corresponded with ectopic rate reductions of 10–82% in the coronary ligation model. SC‐40230 was well tolerated at all doses tested in the conscious dogs. A 5 mg/kg i.v. dose of SC‐40230 converted ouabain‐induced ventricular tachycardias to normal sinus rhythm in anesthetized dogs. The antiarrhythmic effect of SC‐40230 in the ouabain toxicity model was reversed by large (⪇ 240 U) doses of insulin. The experiments described in this study demonstrated that SC‐40230 is a well‐tolerated new class I antiarrhythmic agent with intravenous and oral effectiveness against ventricular arrhythmias.