Effects of procainamide, tocainide and phenytoin on guinea pig cardiac mitochondrial ATPase activity.

The effects of three class I antiarrhythmic drugs procainamide, tocainide and phenytoin on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. Tocainide inhibited the ATPase activity in the range of 1.0 nM-500 mM, exhibiting IC20 and IC50 values of 9.4 +/- 0.7 microM and 5.2 +/- 0.4 mM, while procainamide exhibited significant (p < 0.05) inhibitory effect only at concentrations above 1.0 mM with IC20 and IC50 values of 35.4 +/- 2.7 mM and 90.8 +/- 3.7 mM, respectively. On the other hand, phenytoin inhibited the enzyme by 17% and 8% at 1.0 nM and 1.0 microM respectively, while it stimulated it at higher concentrations, thereby increasing its activity by 10%, 57% and 227% at 10, 100, 1000 microM, respectively. The inhibitory actions of these drugs are probably related to their lipophilicity and membrane stabilizing activity, while the stimulatory effect of phenytoin suggests some specific interaction with some component(s) of the oxidative phosphorylation or respiratory chain.