Diuretics and transmembrane ionic exchanges: structure-activity relations and clinical applications

Abstract

The study of membrane ion transport has facilitated the discovery of potent and quite specific inhibitory drugs. Some of these compounds are therapeutic agents acting on basic transport mechanisms as in the case of the cardiac glycosides on the myocardial sodium ion (Na +), potassium ion (K +) pump, and the loop diuretics on the renal Na +, K +, chloride (Cl −) co-transport system. The development of inhibitors for other transport systems such as Na +/hydrogen ion (H +), Na +/calcium ion (Ca 2+) and bicarbonate ( HCO 3 −) Cl − exchangers requires the screening of a large number of molecules. For several reasons, the human red blood cell is one of the best models for screening the effect of drugs on ion transport mechanisms. The use of human red cells for pharmacologic studies of ion transport has increased the understanding of the structure-activity relations of diuretics. For in stance, loop diuretics that are chemically neutral were considered for many years as drugs that act similarly to classic acid loop diuretics. They are now considered as potent inhibitors of ( HCO 3 −) Cl − anion exchange. A brief summary of the more recent results is given together with the perspectives of new fundamental and therapeutic applications of these compounds.