PT  - JOURNAL ARTICLE
AU  - Baer, J. E.
AU  - Jones, C. B.
AU  - Spitzer, S. A.
AU  - Russo, H. F.
TI  - THE POTASSIUM-SPARING AND NATRIURETIC ACTIVITY OF N-AMIDINO-3,5-DIAMINO-6-CHLOROPYRAZINECAR-BOXAMIDE HYDROCHLORIDE DIHYDRATE (AMILORIDE HYDROCHLORIDE)
DP  - 1967 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 472--485
VI  - 157
IP  - 2
4099  - http://jpet.aspetjournals.org/content/157/2/472.short
4100  - http://jpet.aspetjournals.org/content/157/2/472.full
SO  - J Pharmacol Exp Ther1967 Aug 01; 157
AB  - 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. © 1967 by The Williams & Wilkins Company