COMPARATIVE EFFECTS OF PROCAINAMIDE, TOCAINIDE AND LORCAINIDE ON NA+-K+-ATPASE IN GUINEA-PIG HEART PREPARATIONS

1. The effects of three class 1 antiarrhythmic drugs procainamide (class 1A), tocainide (class 1B) and lorcainide (class 1C) on microsomal Na+-K+-ATPase activity were compared with those of ouabain in guinea pig heart preparations. 2. All three antiarrhythmic drugs exhibited concentration-dependent inhibitory actions on the enzyme activity in a fashion similar to that of ouabain. 3. The rank order of their potencies showed the following tendency: lorcainide >> tocainide > procainamide. However, while the actions of lorcainide were comparable to those of cardiotonic steroids, those of procainamide became significant only at concentrations above 80-mu-M. 4. The IC50 values were 1.8 +/- 0.5-mu-M for ouabain, 14.6 +/- 3.4-mu-M for lorcainide, 2.8 +/- 0.7 mM for tocainide and 6.7 +/- 1.1 mM for procainamide. 5. The results demonstrate that these antiarrhythmic agents inhibit the ouabain-sensitive myocardial Na+-K+-ATPase activity in vitro with comparatively varying potencies. 6. These interactions may be pertinent to the proarrhythmic or arrhythmogenic effects of the class 1 type of antiarrhythmic drugs.