The Metabolic Fate of ο-Chloro-α-(tert-butylaminomethyl)-benzyl Alcohol Hydrochloride (C-78). III. In Vitro Metabolism in Rat Liver

Abstract

Rat liver preparation metabolized ο-chloro-α-(tert-butylaminomethyl)-benzyl alcohol hydrochloride (C-78) to 4-hydroxy-C-78 (II), 3-hydroxy-C-78 (III), 1-(ο-chlorophenyl)-1, 2-ethanediol (V), and ο-chloromandelic acid (VI), as in in vivo experiments. Further, two metabolites, 5-hydroxy-C-78 (VII) and 1-(ο-chlorophenyl)-2-aminoethanol (VIII) were newly obtained from in vitro system. However, 4-hydroxy-5-methoxy-C-78, a major metabolite in vivo, was not detected. The microsomal fraction had all the activity for forming the metabolites in the presence of NADPH-generating system. Two types of the reaction by the microsomal fraction, such as ring hydroxylation (major) and cleavage of the side chain (minor), were differently affected by inhibitors, and this fact suggested that both reactions were catalyzed by different enzyme systems.