INFLUENCE OF LORCAINIDE ON MICROSOMAL NA+,K+-ATPASE IN GUINEA-PIG ISOLATED HEART PREPARATIONS

1 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. 2 Both ouabain and lorcainide inhibited the microsomal Na+, K+-ATPase activity in a concentration-dependent fashion. Their inhibitory effective ranges were 0.05-100-mu-M and 0.15-125-mu-M respectively, and the concentrations for half maximal inhibition (IC50 values) were 2.1 +/- 0.3 and 33.5 +/- 7.3-mu-M, respectively. 3 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. 4 The present study demonstrates that lorcainide is a potent inhibitor of myocardial Na+, K+-ATPase.