Metabolism of sumatriptan revisited
Abstract Scientific 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 HP...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.1051 |
| _version_ | 1811165291755864064 |
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| author | Timo Pöstges Matthias Lehr |
| author_facet | Timo Pöstges Matthias Lehr |
| author_sort | Timo Pöstges |
| collection | DOAJ |
| description | Abstract Scientific 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 into N‐desmethyl sumatriptan, which was further demethylated to N,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 the N‐demethylated and the N,N‐didemethylated derivatives. |
| first_indexed | 2024-04-10T15:34:53Z |
| format | Article |
| id | doaj.art-c6dd6de221714b1ab7f880556aafdcf4 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-04-10T15:34:53Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-c6dd6de221714b1ab7f880556aafdcf42023-02-13T07:58:31ZengWileyPharmacology Research & Perspectives2052-17072023-02-01111n/an/a10.1002/prp2.1051Metabolism of sumatriptan revisitedTimo Pöstges0Matthias Lehr1Institute of Pharmaceutical and Medicinal Chemistry University of Münster Münster GermanyInstitute of Pharmaceutical and Medicinal Chemistry University of Münster Münster GermanyAbstract Scientific 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 into N‐desmethyl sumatriptan, which was further demethylated to N,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 the N‐demethylated and the N,N‐didemethylated derivatives.https://doi.org/10.1002/prp2.1051cytochrome P450metabolismmonoamine oxidasesumatriptanzolmitriptan |
| spellingShingle | Timo Pöstges Matthias Lehr Metabolism of sumatriptan revisited Pharmacology Research & Perspectives cytochrome P450 metabolism monoamine oxidase sumatriptan zolmitriptan |
| title | Metabolism of sumatriptan revisited |
| title_full | Metabolism of sumatriptan revisited |
| title_fullStr | Metabolism of sumatriptan revisited |
| title_full_unstemmed | Metabolism of sumatriptan revisited |
| title_short | Metabolism of sumatriptan revisited |
| title_sort | metabolism of sumatriptan revisited |
| topic | cytochrome P450 metabolism monoamine oxidase sumatriptan zolmitriptan |
| url | https://doi.org/10.1002/prp2.1051 |
| work_keys_str_mv | AT timopostges metabolismofsumatriptanrevisited AT matthiaslehr metabolismofsumatriptanrevisited |