The Actions of Synthetic Salicyluric Acid

Abstract

The occurrence of a natural salicyluric acid in the body, and its significance as a detoxification product, after administration of salicylates, analogous to hippuric acid after benzoates, have been much discussed but not conclusively settled. Owing to previous negative results by one of us 1 with chemical methods of isolation from urines, it was attempted to obtain indirect evidence on the question by a study of the pharmacological actions of synthetic salicyluric acid. The pure compound was synthesized according to E. Fischer's method 2 by Dr. Robert T. Dillon of the California Institute of Technology, Pasadena, to whom our thanks are due.∗

It was found that synthetic salicyluric acid was comparatively stable in vitro, since it was not hydrolyzed in incubated buffer-salt solutions with hydrion concentrations falling within the range of body fluids, and in these solutions containing ferments, yeast and bile-salts. Some hydrolysis occurred in solutions of pH 2 and 14 and complete hydrolysis in strong acids and alkalies.

On the other hand, the compound suffered marked hydrolysis in its passage through the body, since from one-half to three-fourths of the total excreted salicyl in urines of human subjects (6) consisted of ordinary salicylate. The total salicyl excretion was about 88% of the total administered (from 4 to 28 gm.). The effects on urinary nitrogenous metabolites were variable or insignificant. The symptoms of salicylism in human subjects were weak, even with the highest oral doses, but in white mice, white rats, pigeons and a dog (total, 89 animals) typical symptoms of salicyl poisoning were demonstrated after hypodermic and intravenous administrations. The M.F.D. in the majority or 60% of the mice was 1.13 gm., and in rats 3 gm., per kilo.