INVESTIGATION OF CLASS-I ANTIARRHYTHMIC DRUG ACTIONS ON GUINEA-PIG CARDIAC MITOCHONDRIAL LACTATE-DEHYDROGENASE ACTIVITY

1. The effects of the Class I anti-arrhythmic drugs quinidine, procain amide, lidocaine, phenytoin and tocainide on mitochondrial lactate deh ydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration -dependent fashion, exhibiting varying profiles in their actions. Lido caine exhibited inhibitory concentration 20% (IC20) and IC50 values of 0.52 +/- 0.02 mmol/L and 25.6 +/- 0.5 mmol/L, procainamide 6.0 +/- 0. 2 mmol/L and 108 +/- 7.2 mmol/L, phenytoin 3.4 +/- 0.06 mumol/L and 0. 34 +/- 0.02 mmol/L, quinidine 39.2 +/- 1.2 mumol/L and 9.8 +/- 0.8 mmo l/L and tocainide 2.7 +/- 0.3 mmol/L and 44.6 +/- 2.5 mmol/L. 3. Accor ding to the IC50 values, this is the order of their inhibitory potenci es: phenytoin > quinidine > lidocaine > tocainide > procainamide. This trend is in general agreement with the lipophilicity rank of the drug s. 4. It is concluded, therefore, that inhibition of mitochondrial lac tate dehydrogenase is a property shared by most Class I anti-arrhythmi c drugs which may depend on their lipophilicity and possibly their mem brane stabilizing effects.