Metabolism of sumatriptan revisited

Proposed metabolic pathway of sumatriptan. AbstractScientific literature describes that sumatriptan is metabolized by oxidative deamination of its dimethylaminoethyl residue by monoamine oxidase A (MAO A) and not by cytochrome P450 (CYP)-mediated demethylation, as is usual for such structural elements. Using recombinant human enzymes and HPLC-MS analysis, we found that CYP enzymes may also be involved in the metabolism of sumatriptan. The CYP1A2, CYP2C19, and CYP2D6 isoforms converted this drug intoN-desmethyl sumatriptan, which was further demethylated toN,N-didesmethyl sumatriptan by CYP1A2 and CYP2D6. Otherwise, sumatriptan and its two desmethyl metabolites were metabolized by recombinant MAO A but not by MAO B to the corresponding acetaldehyde, with sumatriptan being only a poor substrate for MAO A compared to theN-demethylated and theN,N-didemethylated derivatives.
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research