Interaction of bretylium tosylate with guinea-pig myocardial Na(+)-K(+)-ATPase.

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Dzimiri N, Almotrefi AA

Interaction of bretylium tosylate with guinea-pig myocardial Na(+)-K(+)-ATPase.

Gen Pharmacol. 1991;22(5):935-8.

PubMed ID

1662173 [ View in PubMed

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Abstract

1. The effects of bretylium on myocardial Mg(2+)-dependent, Na(+)-K(+)-ATPase (EC 3.6.1.3) activity were compared with those of ouabain in guinea-pig heart preparations. 2. Both ouabain and bretylium inhibited microsomal Na(+)-K(+)-ATPase activity in a concentration-dependent fashion in the range of 0.01-100 and 1.0-4000 microM, respectively. The IC50 values were 1.93 +/- 0.27 microM for ouabain and 2.45 +/- 0.17 mM for bretylium. 3. In another set of experiments, the effects of bretylium on the enzyme activity were tested in combination with 2.5 or 5.0 microM ouabain. 4. The combined effects of the two drugs resulted in a net reduction in the total inhibitory activities of the individual drugs, which became more marked the higher the bretylium concentration. This trend seems to suggest a competitive mode of interaction of the two drugs in their inhibitory actions on Na(+)-K(+)-ATPase activity. 5. The results demonstrate therefore that bretylium is a potent inhibitor of ouabain-inhibited ATP hydrolysis by myocardial Na(+)-K(+)-ATPase. These actions may be pertinent with regard to some of its cardiac actions.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bretylium	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Yes	Inhibitor	Details