OXIDATION OF P-(N1-METHYLHYDRAZINO METHYL)-N-ISOPROPYL BENZAMIDE (PROCARBAZINE) TO METHYLAZO DERIVATIVE AND OXIDATIVE CLEAVAGE OF N2-C BOND IN ISOLATED PERFUSED RAT LIVER

The oxidation of p-(N1-methylhydrazino methyl)-N-isopropyl benzamide (procarbazine, Natulan) to its azo-derivative (AZO) and the formation of the main inactive metabolite terephthalic acid isopropylamide (TAC) has been studied in the isolated perfused rat liver. In this system, procarbazine was oxidized to AZO at a rate of about 28 μmoles/hr as calculated for 100 g body weight, whereas TAC was produced at a 4-fold lower rate (7 μmoles/hr per 100 g body weight). This results in an accumulation of the lipophilic, cytostatically active AZO. The effect of SKF 525-A, as well as 3-methyfcholanthrene, on the rate of TAC production and AZO disappearance indicates that the N2-C bond of AZO is split by a microsomal hydroxylase. Methyldiimine, which is the theoretically expected product of this reaction beside p-formyl-N-isopropyl benzamide, is discussed as the possible source of methyl radicals. Such radicals have been suggested by others to be responsible for the cytostatic eifect of procarbazine. © 1969.