Abstract
1.
1. The effects of three class I antiarrhythmic drugs quinidine, lidocaine and lorcainide on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase, EC 3.6.1.3] activity were evaluated in guinea pig heart preparations.
2.
2. All three drugs inhibited the enzyme activity in a concentration-dependent fashion.
3.
3. Lorcainide was the most potent, exerting inhibitory effects in the range of less than 1.0 nM-2.0 mM, with IC
20 and IC
50 values of 9.4 ± 0.6 nM and 87.2 ± 5.5
μM. However, in the range of approx. 10 nM-10 μM, the enzyme response decreased only slightly with increasing lorcainide concentrations.
4.
4. Quinidine and lidocaine, on the other hand, inhibited the enzyme activity in the range of 1.0 μM-100 mM.
5.
5. The IC
20 and IC
50 values for quinidine were 0.92 ± 0.04 mM and 4.8 ± 0.6 mM and for lidocaine were 115 ± 6
μM and 2.3 ± 0.3 mM.
6.
6. The results show that all three drugs inhibit mitochondrial ATPase activity and that lorcainide is the most potent.
7.
7. These inhibitory effects may be related to the lipophilicity and membrane stabilizing activity of this class of antiarrhythmic drugs.