ArticleJournal of natural medicines2025
Metabolism of coclaurine into the WADA-banned substance higenamine: a doping-relevant analytical evaluation of Kampo extracts.
Article in Journal of natural medicines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Annual Banned-Substance Review 18th Edition-Analytical Approaches in Human Sports Drug Testing 2024/2025.Drug testing and analysis · 2026Review
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9 authors.
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Abstract
Higenamine, a β2-agonist, has been listed as a prohibited substance by the World Anti-Doping Agency (WADA) since 2017, poses a doping risk through the use of traditional herbal formulations. In Japan, Kampo medicines, composed of multiple crude drugs, are widely used, raising concerns about the unintentional intake of banned substances. In this study, urinary excretion of higenamine was observed in mice following coclaurine administration, and higenamine formation was confirmed in human liver microsomes, indicating a potential risk associated with coclaurine-containing herbs. Therefore, 128 Kampo extract products were analyzed to identify crude drugs containing higenamine and/or coclaurine using lateral flow immunoassay (LFA), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Consequently, fourteen crude drugs were identified to contain higenamine and/or coclaurine. Notably, six crude drugs-including Magnolia bark, Japanese Zanthoxylum peel, Jujube seed, Magnolia flower, Cimicifuga rhizome, and Coptis rhizome-were newly confirmed to contain higenamine, while nine-including Cinnamon bark, Magnolia bark, Euodia fruit, Asiasarum root, Japanese Zanthoxylum peel, Cimicifuga rhizome, Jujube, Processed Aconite root, and Phellodendron bark-were newly identified as containing coclaurine. These results underscore the potential risk of doping violations associated with coclaurine, which may be metabolized into higenamine, although coclaurine is not currently classified as a prohibited substance. Our findings highlight the need for regulatory consideration to mitigate unintentional doping risks among athletes using Kampo medicine.
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