The Formation of an N-Hydroxymethyl Intermediate in the N-Demethylation of N-Methylcarbazole in vivo and in vitro

Abstract

1. The metabolism of N-methylcarbazole has been studied in several mammalian species, both in vivo and in vitro.

2. An important metabolite after incubation of N-methylcarbazole with liver microsomes in vitro was identified as N-hydroxymethylcarbazole.

3. This metabolite was also found as a conjugate (probably the O-glucuronide) in the urine of some species.

4. N-Hydroxymethylcarbazole decomposed spontaneously in solution at pH 7.4 to formaldehyde and carbazole; this breakdown was enhanced by incubation with liver microsomes from several species, especially the guinea-pig.

5. The role of N-methyl hydroxylation, compared with N-oxidation, in the mechanism of N-dealkylation of non-basic N-methyl compounds is discussed.