Metabolism of N′-(4-chloro- o-tolyl)- N, N-dimethyl-formamidine (chlorphenamidine) and 4′-chloro- o-formotoluidide by rat hepatic microsomal and soluble enzymes

Abstract

1. 1. The metabolism of chlorphenamidine- 14C acaricide and its primary hydrolysis product 4′-chloro- o-formotoluidide- 14C by rat hepatic enzymes in vitro was studied. 2. 2. Demethylchlorphenamidine formed by microsomal N-demethylase action was the major chlorphenamidine metabolite; the system required molecular oxygen and exogenous NADPH to effect this conversion which was inhibited by SKF-525A. 3. 3. Rat liver soluble fraction contained a DFP-sensitive hydrolase that deformylated 4′-chloro- o-formotoluidide to 4-chloro- o-toluidine and probably N-formyl-5-chloro-anthranilic acid to 5-chloroanthranilic acid; it was speculated that this enzyme was formamidase (E.C. 3.5.1.9). 4. 4. Chlorphenamidine metabolites formed in vitro were qualitatively similar to those detected in urine from chlorphenamidine-treated mammals in other studies.