STUDIES OF THE URICOGENIC EFFECT OF 2-SUBSTITUTED THIADIAZOLES IN MAN*

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Abstract
2-Ethylamino-l,3, 4-thiadiazole and the 2-amino- and 2-acetylamino analogs caused an increase in de novo uric acid synthesis, demonstrated by parallel increase in uric acid in blood and urine, by increase in incorporation of sodium formate-C14 and ammonia-N15 into uric acid and by decrease in the concentration of uric acid-C14 derived from previously administered adenine-Cl4. The related 2,5-substituted thiadiazoles did not have a uricogenic effect. The uricogenic effect of the 2-substituted thiadiazoles could be blocked by nicotinamide, which also prevented the associated glossitis and by the glutamine antagonists, o-diazo-acetyl-L-serine and 6-diazo-5-oxo-L-norleucine which did not prevent the glossitis. It is postulated that the thiadiazoles act by blocking the incorporation of newly synthesized purine molecules into coenzymes and/or purine polynucleotides, with a resultant compensatory esaggeration of de novo purine biosynthesis leading to increased uric acid production.