Contribution of Aldehyde Oxidizing Enzymes on the Metabolism of 3,4-Dimethoxy-2-phenylethylamine to 3,4-Dimethoxyphenylacetic Acid by Guinea Pig Liver Slices

Abstract

Background/Aims: 3,4-Dimethoxy-2-phenylethylamineis catalyzed to its aldehyde derivative by monoamineoxidase B, but the subsequent oxidation into thecorresponding acid has not yet been studied.Oxidation of aromatic aldehydes is catalyzed mainlyby aldehyde dehydrogenase and aldehyde oxidase.Methods: The present study examines the metabolismof 3,4-dimethoxy-2-phenylethylamine in vitro and infreshly prepared and cryopreserved guinea pig liverslices and the relative contribution of differentaldehyde-oxidizing enzymes was estimated bypharmacological means. Results: 3,4-Dimethoxy-2-phenylethylamine was converted into thecorresponding aldehyde when incubated withmonoamine oxidase and further oxidized into the acidwhen incubated with both, monoamine oxidase andaldehyde oxidase. In freshly prepared and cryopreserved liver slices, 3,4-dimethoxyphenylaceticacid was the main metabolite of 3,4-dimethoxy-2-phenylethylamine. 3,4-Dimethoxyphenylacetic acidformation was inhibited by 85% from disulfiram(aldehyde dehydrogenase inhibitor) and by 75-80%from isovanillin (aldehyde oxidase inhibitor), whereasallopurinol (xanthine oxidase inhibitor) inhibited acidformation by only 25-30%. Conclusions: 3,4-Dimethoxy-2-phenylethylamine is oxidized mainly toits acid, via 3,4-dimethoxyphenylacetaldehyde, byaldehyde dehydrogenase and aldehyde oxidase witha lower contribution from xanthine oxidase.