PT  - JOURNAL ARTICLE
AU  - D J Tweedie
AU  - M D Burke
TI  - Metabolism of the beta-carbolines, harmine and harmol, by liver microsomes from phenobarbitone- or 3-methylcholanthrene-treated mice. Identification and quantitation of two novel harmine metabolites.
DP  - 1987 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 74--81
VI  - 15
IP  - 1
4099  - http://dmd.aspetjournals.org/content/15/1/74.short
4100  - http://dmd.aspetjournals.org/content/15/1/74.full
SO  - Drug Metab Dispos1987 Jan 01; 15
AB  - This study extends an investigation of the metabolism of the beta-carbolines, harmine and harmol, by untreated, phenobarbitone-induced, or 3-methylcholanthrene (MC)-induced mouse liver microsomes to identify two MC-inducible metabolites of harmine and to quantitate their rates of formation using 3H-labeled substrate. An HPLC system was devised to separate harmine and its metabolites. The major metabolite with MC-induced microsomes was identified by mass spectroscopy and by NMR to be 6-hydroxy-7-methoxyharman and was produced at an initial reaction rate of 11 nmol/min/mg of microsomal protein (27-fold induction). The other novel metabolite, 3- or 4-hydroxy-7-methoxyharman (the position of the hydroxyl group could not be definitively assigned by NMR) was produced at an initial reaction rate of 3.8 nmol/min/mg of microsomal protein (32-fold induction) which was similar to the rate of formation of the other metabolite, harmol, determined previously. All three metabolites were further metabolized to unidentified metabolites. Protein binding of [3H]harmine and [3H]harmol was measured and shown to be metabolism dependent. It was also noted that the alkali conditions used for optimal extraction stimulated the protein binding.