THE POTASSIUM-SPARING AND NATRIURETIC ACTIVITY OF N-AMIDINO-3,5-DIAMINO-6-CHLOROPYRAZINECAR-BOXAMIDE HYDROCHLORIDE DIHYDRATE (AMILORIDE HYDROCHLORIDE)

N-amidino-3-amino-6-chloropyrazinecarboxamide enhanced Na + excretion and decreased K + excretion in normal and adrenalectomized rats (Glitzer and Steelman, 1965). The 5-dimethylamino and 5-amino analogs are 3 and 15 times as potent natriuretics orally in normal rats. The latter (amiloride) markedly enhanced Na + excretion and depressed K + excretion in acetazolamide- or hydrochlorothiazide-treated rats. An intravenous dose of 1.0 mg/kg of amiloride in dogs gave a modest (170 µEq/min) but sustained (up to 4 hr) natriuresis; in KCl - or thiazide-treated dogs, K + excretion was inhibited by amiloride. Orally, amiloride increased Na + (but not K + ) excretion at 0.016 to 4.0 mg/kg in dogs; especially at the higher doses, the action lasted more than 6 hr. Amiloride was slowly excreted unchanged by rat, dog and man. Stop-flow studies showed that amiloride increased concentration of Na + and decreased K + and pH of distal tubular samples, with no change in Cl - . The mode of the K + -sparing action appears to differ from those of the aldosterone antagonists or organomercurial diuretics.