The formation of an N-hydroxymethyl intermediate in the N-demethylation of N-methylcarbazole in vivo and in vitro.

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.