Inhibition of Rabbit Liver Mitochondrial Monoamine Oxidase by New Hydrazine Derivatives. III. Secondary Action of the Compounds 31037-S and 31087-S on the Preincubated Enzyme

Abstract

Additional effects of 1-benzyl-2-(4, 5, 6, 7-tetrahydro-1, 2-benzisoxazol-3-yl) carbonylhydrazine hydrochloride (31037-S) and 1-benzyl-2-(3-methylisoxazol-5-yl) carbonylhydrazine (31087-S) were demonstrated in the mitochondrial monoamine oxidase of rabbit liver. The potencies of the compounds were greatly enhanced when the enzyme was preincubated for a long time at 37.5° before the addition of substrate and each hydrazine compound. This phenomenon occurred proportionally to time of the preincubation. Although the potenciated effect was observed analogously with both hydrazine compounds, it was much more remarkable in the case of 31087-S, especially when the enzyme was preincubated with semicarbazide. The preincubation did not influence normal enzyme activity. The compounds affected competitively the 3 min-preincubated enzyme, while they showed a non-competitive type inhibition in the 10 min-preincubated one. The phenomena observed here were unlikely based on mechanisms such as the transformation of each inhibitor, damage of the mitochondrial structure or the sensitization of the enzyme by cyanide.