Potassium-Retaining Diuretics: Amiloride

Abstract

Amiloride was discovered in the late 1960s during an extensive screening process at the Merck Sharp and Dohme Research Laboratories. Starting with N-amidino-3-amino-6-bromopyrazinecarboxamide, over 300 compounds were tested for their ability to reverse the effects of mineralocorticoids in rats (Bicking et al. 1965). Of these amiloride was among the most potent in producing natriuresis without a concomitant kaliuresis. Since then over 1000 different analogs have been synthesized and studied (Kleyman and Cragoe 1988).