Cm. Dixon et al., CHARACTERIZATION OF THE ENZYME RESPONSIBLE FOR THE METABOLISM OF SUMATRIPTAN IN HUMAN LIVER, Biochemical pharmacology, 47(7), 1994, pp. 1253-1257
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.