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Journal of Pharmacology and Experimental Therapeutics

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Research ArticleArticle

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

J. E. Baer, C. B. Jones, S. A. Spitzer and H. F. Russo
Journal of Pharmacology and Experimental Therapeutics August 1967, 157 (2) 472-485;
J. E. Baer
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C. B. Jones
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S. A. Spitzer
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H. F. Russo
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Abstract

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.

Footnotes

    • Received December 14, 1966.
    • Accepted February 20, 1967.
  • © 1967 by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 157, Issue 2
1 Aug 1967
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Research ArticleArticle

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

J. E. Baer, C. B. Jones, S. A. Spitzer and H. F. Russo
Journal of Pharmacology and Experimental Therapeutics August 1, 1967, 157 (2) 472-485;

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Research ArticleArticle

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

J. E. Baer, C. B. Jones, S. A. Spitzer and H. F. Russo
Journal of Pharmacology and Experimental Therapeutics August 1, 1967, 157 (2) 472-485;
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