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European Heart Journal 1992 13(Supplement G):22-27; doi:10.1093/eurheartj/13.suppl_G.22
Copyright © 1992 by the European Society of Cardiology.
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© 1992 The European Society of Cardiology

Modulation of electrolyte excretion by potassium retaining diuretics

T. Netzer, H. Knauf and E. Mutschler

Department of Pharmacology, University of Frankfurt/Main Germany

Correspondence: T. Netzer, Department of Pharmacology, University of Frankfurt Main, Germany

Triamterene and amiloride belong to the potassium retaining diuretics of the cycloamidine type. These agents exert natriuretic as well as antikaliuretic effects. After administration of high doses an additional magnesium-sparing property also becomes evident.

Whereas amiloride is only metabolized to a minor extent, triamterene is rapidly bio-transformed to the phase-I metabolite, hydroxytriamterene, and the phase-II metabolite, hydroxytriamierene sulphuric acid ester. This acidic phase-II metabolite is still diuretically active, but its electrolyte excretion profile is different the parent compound: although the natriuretic properties are not altered, the potassium retention is very weak.

Further studies in rats with cycloamidine derivatives of the triamterene type containing neutral, acidic or basic side chains at the phenyl moiety as well as with basic pteridine derivatives, revealed further evidence that the natriuretic, antikaliuretic and antimagnesiuretic effects can be influenced almost independently by structural variations of the parent drug. Thus, it was possible to obtain compounds predominantly increasing sodium excretion without affecting potassium or magnesium excretion. On the other hand, substances could be developed with mainly antikaliuretic effects, or compounds, which enhanced sodium and reduced magnesium excretion and did not interfere with the potassium elimination. Based on these findings, it can be concluded that distal tubular transport of sodium, potassium and magnesium may be influenced independently from each other. These renal effects of triamterene and its derivatives seem to be independent of their antiarrhythmic actions, as suggested by recent studies.

Key Words: Antiarrhythmics • diuretics • potassium-sparing • magnesium-sparing • pteridine derivatives


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