THE EFFECTS OF THE STEREOISOMERS OF PROPAFENONE AND DIPRAFENONE IN GUINEA-PIG HEART

1 Optically pure enantiomers of propafenone and diprafenone were prepared from their racemic mixtures and tested for their ability to block beta-adrenoceptors and to prolong functional refractory period in the guinea-pig heart. beta-Adrenoceptor affinity of the enantiomers was determined by the radioligand binding technique and in functional experiments. 2 Propafenone and diprafenone inhibited specific binding of the beta-adrenoceptor antagonist (-)-[H-3]-CGP-12177 to guinea-pig myocardial membranes. beta-Adrenoceptor affinities of diprafenone enantiomers exceeded those of corresponding propafenone enantiomers by one order of magnitude. Displacement of (-)-[H-3]-CGP-12177 by both antiarrhythmics was highly stereoselective, in that the (S)-enantiomers were 40-60 fold, i.e. 1.6-1.8 log units more potent than the (R)-enantiomers. 3 Propafenone and diprafenone antagonized the positive inotropic action of isoprenaline in isolated atria. beta-Adrenoceptor antagonist potencies of diprafenone enantiomers were about one order of magnitude higher than those of corresponding propafenone enantiomers. For both drugs the (S)-enantiomer was found to be considerably more potent (14-40 fold) than the (R)-enantiomer. 4 Propafenone and diprafenone prolonged functional refractory period of isolated auricles with equal potency and no difference in the antiarrhythmic activity of purified enantiomers was found. 5 It is concluded that the enantiomers of propafenone and diprafenone exert comparable antiarrhythmic activity, whereas only (S)-enantiomers block cardiac beta-adrenoceptors with high affinity, which explains the beta-adrenoceptor antagonist effects of the racemic drugs.