Resolution of flecainide acetate, N-(2-piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzam ide acetate, and antiarrhythmic properties of the enantiomers

Abstract

The antiarrhythmic agent flecainide acetate was resolved by fractional crystallization of its diastereomeric alpha-bromocamphor-pi-sulfonate salts. Optical purity of the two enantiomers was shown to be greater than 99% by an NMR technique using the chiral shift reagent Eu(hfbc)3. Antiarrhythmic effects of flecainide and its enantiomers were assessed in two different animal models, chloroform-induced ventricular fibrillation in mice and ouabain-induced ventricular tachycardia in dogs. The two enantiomers were highly effective in suppressing both of these experimental arrhythmias and appeared to be essentially equipotent. No significant differences were found either between the two enantiomers or between the enantiomers and racemic flecainide.