CHARACTERIZATION OF THE ENZYME RESPONSIBLE FOR THE METABOLISM OF SUMATRIPTAN IN HUMAN LIVER

Studies have been undertaken to investigate the enzymes responsible fo r the metabolism of [C-14]sumatriptan in man. Oxidative deamination of sumatriptan to form the indole acetic acid derivative is the only pha se 1 pathway evident in man and both cytochrome P450 (P450) and monoam ine oxidase (MAO) are capable of catalysing this type of reaction. The metabolism of [C-14]sumatriptan was therefore investigated in vitro i n a preparation derived from human Liver, which was shown, by the use of the probe substrates [C-14]testosterone (P350), [H-3]5HT (MAO-A) an d [C-14]benzylamine (MAO-B) to be a rich source of both enzyme systems . Incubation with clorgyline and deprenyl, probe inhibitors of MAO-A a nd MAO-B, respectively, showed that [C-14]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 th e major enzyme responsible for the metabolism of sumatriptan in human liver.