Inhibition of Rabbit Liver Mitochondrial Monoamine Oxidase by New Hydrazine Derivatives. I. Active Moieties of the Compounds 31037-S and 31087-S

Abstract

The effects of hydrazine compounds on rabbit liver mitochondrial monoamine oxidase were examined using a manometric method. Two hydrazine derivatives, i.e., 1-benzyl-2-(4, 5, 6, 7-tetrahydro-1, 2-benzisoxazol-3-yl) carbonyl hydrazine hydrochloride (31037-S) and 1-benzyl-2-(3-methylisoxazol-5-yl) carbonyl hydrazine (31087-S) were especially powerful inhibitors of this enzyme. They acted competitively with the enzyme and were more potent than iproniazid. When each inhibitor was allowed to react with the enzyme in the absence of substrate, its inhibitory action was irreversible and much enhanced. Cyanide and oxygen promoted the inhibitory action of both compounds. In comparison with the potencies of some allied compounds, it was suggested that an active part of 31037-S or 31087-S is a benzylhydrazine moiety, and that it directly influences the enzyme active site.