Influence of lorcainide on microsomal Na⁺, K⁺‐ATPase in guinea‐pig isolated heart preparations

Abstract

The effects of lorcainide on the myocardial Mg2+‐dependent, Na+ and K+‐activated adenosine triphosphatase (Na+, K+‐ATPase) were compared in guinea‐pig heart preparations with those of ouabain, a specific inhibitor of the enzyme activity. Both ouabain and lorcainide inhibited the microsomal Na+, K+‐ATPase activity in a concentration‐dependent fashion. Their inhibitory effective ranges were 0.05–100 μm and 0.15–125 μm respectively, and the concentrations for half maximal inhibition (IC50 values) were 2.1 ± 0.3 and 33.5 ± 7.3 μm, respectively. In a second series of experiments, the combined effects of the two drugs on the enzyme activity were studied. In these experiments, lorcainide produced a concentration‐dependent potentiation of the inhibitory effects of ouabain on Na+, K+‐ATPase activity. The present study demonstrates that lorcainide is a potent inhibitor of myocardial Na+, K+‐ATPase.

Variations in potassium concentration modify the inhibitory effect of lorcainide on myocardial Na+‐K+‐ATPase activity

“…Lorcainide, like most antiarrhythmic agents in current use, shares this proarrhythmic property (Podrid et al, 1987;Levine et al, 1989). In a recent study (Almotrefi & Dzimiri, 1991a), we have shown that lorcainide is a potent inhibitor of the adenosine 5'-triphosphate (ATP)-hydrolytic action of myo-cardial Na'-K+-ATPase. The implication of this finding with regard to the drug's mode of action is not completely clear.…”