New Inhibitors of Alcohol Dehydrogenase: Studies in Vivo and in Vitro in the Rat

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Abstract
Two compounds bearing an amide group, p-butoxyphenyl acetamide (BPA) and N-(p-butoxybenzyl)formamide (BBF) were studied as inhibitors of alcohol dehydrogenase (ADH) and their action compared with that of 4-methylpyrazole (4-MP), a known inhibitor of this enzyme. In vitro studies on pure horse liver ADH showed that BPA and BBF were noncompetitive inhibitors with respect to ethanol and that their Ki [inhibitory constant] values were 22 and 0.14 .mu.m, respectively. The apparent Ki values of BPA and BBF for the rat liver ADH were 90 and 2.3 .mu.m, respectively (noncompetitive inhibition). Several in vivo experiments were carried out in the rat. Administration i.p. of the substances (460 .mu.mol/kg) 1 h before i.p. injection of alcohol (2 g/kg body wt) led to a significant decrease in ethanol catabolism. Injection of the substances at 460 .mu.mol/kg brought about a decrease in rat liver ADH activity, but the activity of mitochondrial aldehyde dehydrogenase was only decreased in animals treated with BBF.