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Journal of Pharmacology And Experimental Therapeutics, Vol. 83, Issue 4, 235-249, 1945
Copyright © 1945 by American Society for Pharmacology and Experimental Therapeutics

THE MODE OF ACTION OF THREE NEW DIURETICS: MELAMINE, ADENINE AND FORMOGUANAMINE

WERNER L. LIPSCHITZ 1 and EDGAR STOKEY 1

1 From the Lederle Laboratories, Pearl River, New York

1. Melamine, adenine sulfate and formoguanamine, which by the rat assay method were found to be potent diuretics, proved to be active also on the dog. Taking the urea potency as 1 in the dog the activities of the three compounds are in the order of 18.6, 72.5, 145, respectively. These correspond to the rat figures 76.5, 139, 347. The drugs increase the output of NaCl as well as water in proportion to the dose.

2. Melamine is excreted in the dog or rat partly as the crystalline dimelaminemonophosphate. The total can be isolated from the warm urine by precipitation with oxalic acid as the crystalline monomelamine-monooxalate, and 60-86.5 per cent of the melamine fed to dogs was recovered in the urine in 24 hours.

3. Melamine fed in diuretic doses to digitalized cats and dogs does not change the fatal digitalis dose.

4. Diuresis produced specifically by urea, caffeine, melamine, adenine or formoguanamine fed in saline to rats, is little affected by pitressin—in contrast to water diuresis. The hormone, therefore, cannot be considered as the limiting factor which controls xanthine diuresis.

5. No significant toxic effects of the three new diuretics were found when large doses were administered orally or intravenously to rats, rabbits or dogs. This is similar to common experience with urea, and in contrast to the xanthines and the mercury compounds.

Submitted on October 13, 1944




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