RT Journal Article
SR Electronic
T1 THE POTASSIUM-SPARING AND NATRIURETIC ACTIVITY OF N-AMIDINO-3,5-DIAMINO-6-CHLOROPYRAZINECAR-BOXAMIDE HYDROCHLORIDE DIHYDRATE (AMILORIDE HYDROCHLORIDE)
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 472
OP 485
VO 157
IS 2
A1 Baer, J. E.
A1 Jones, C. B.
A1 Spitzer, S. A.
A1 Russo, H. F.
YR 1967
UL http://jpet.aspetjournals.org/content/157/2/472.abstract
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