title: Characterization of the enzyme responsible for the metabolism of sumatriptan in human liver.
abstract: Studies have been undertaken to investigate the enzymes responsible for the metabolism of [14C]sumatriptan in man. Oxidative deamination of sumatriptan to form the indole acetic acid derivative is the only phase 1 pathway evident in man and both cytochrome P450 (P450) and monoamine oxidase (MAO) are capable of catalysing this type of reaction. The metabolism of [14C]sumatriptan was therefore investigated in vitro in a preparation derived from human liver, which was shown, by the use of the probe substrates [14C]testosterone (P450), [3H]5HT (MAO-A) and [14C]benzylamine (MAO-B) to be a rich source of both enzyme systems. Incubation with clorgyline and deprenyl, probe inhibitors of MAO-A and MAO-B, respectively, showed that [14C]sumatriptan was metabolized by MAO-A; there was no evidence of P450 involvement in its metabolism. The data in this study therefore indicate that the enzyme MAO-A is the major enzyme responsible for the metabolism of sumatriptan in human liver.
authors.affiliation: Department of Drug Metabolism III, Glaxo Group Research Ltd, Ware, Herts, U.K.
authors.forename: C M
authors.initials: CM
authors.lastname: Dixon
authors.forename: G R
authors.initials: GR
authors.lastname: Park
authors.forename: M H
authors.initials: MH
authors.lastname: Tarbit
mesh_terms: D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D018170:Sumatriptan / Q000378:metabolism*
chemical_list: D012642:Selegiline; D009249:NADP; D018170:Sumatriptan; D008995:Monoamine Oxidase; D003010:Clorgyline