THE INFLUENCE OF HYDRAZINE AND ITS DERIVATIVES ON METABOLISM I. THE EFFECT OF SUBSTITUTION IN THE HYDRAZINE MOLECULE UPON THE HYPOGLYCEMIC ACTION OF HYDRAZINE

¹ From the Laboratory of Physiological Chemistry of the School of Medicine, University of Michigan, Ann Arbor

1. A series of hydrazine derivatives has been prepared and the influence of these on the concentration of blood sugar in the rabbit has been studied.

2. Hydrazine hydrate and its salts (sulfate, acetate) were found to have nearly equal hypoglycemic effect and toxicity, when the content of hydrazine was comparable. The anion is not considered to influence the action of hydrazine.

3. The following derivatives of hydrazine were demonstrated to produce hypoglycemia in the rabbit: benzoylhydrazine, hippurylhydrazine, s-acetylbenzoylhydrazine, bidimethylazimethylene, isopropylideneacetylhydrazine, and isopropylidenebenzoylhydrazine. The introduction of such acyl radicals as acetyl, malonyl, ethylic carboxyl, hydroxybenzoyl, and hippuryl into the hydrazine molecule decreased the hypoglycemic action. while the introduction of the benzoyl radical increased this action slightly.

4. The introduction of a hydroxyl group into the m- or p-position in benzoylhydrazine decreased both toxicity and hypoglycemic potency, while an o-hydroxyl group decreased the hypoglycemic potency but increased the toxicity.

5. The introduction of thio groups, as thiocarbaminyl and dithioformyl, markedly increased the toxicity of hydrazine. The hypoglycemic effect was lost and a tendency toward the production of hyperglycemia was observed.