{"entity": "publication", "iuid": "cf3c706e06c742b0b48ded9bd9914f5c", "timestamp": "2026-08-22T09:49:07.183Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cf3c706e06c742b0b48ded9bd9914f5c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cf3c706e06c742b0b48ded9bd9914f5c"}}, "title": "Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies.", "authors": [{"family": "Yusof", "given": "Siti R", "initials": "SR", "orcid": "0000-0003-2257-9933", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51e1c006c0464ac49e6d56c716799782.json"}}, {"family": "Mohd Uzid", "given": "Mahathir", "initials": "M"}, {"family": "Teh", "given": "Eng-Huat", "initials": "EH"}, {"family": "Hanapi", "given": "Nur Aziah", "initials": "NA"}, {"family": "Mohideen", "given": "Mazlin", "initials": "M"}, {"family": "Mohamad Arshad", "given": "Ahmad Saifuddin", "initials": "AS"}, {"family": "Mordi", "given": "Mohd Nizam", "initials": "MN"}, {"family": "Loryan", "given": "Irena", "initials": "I", "orcid": "0000-0002-1557-4416", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8373a9e8e10a48b7904075577f7a15e6.json"}}, {"family": "Hammarlund-Udenaes", "given": "Margareta", "initials": "M"}], "type": "journal article", "published": "2019-09-00", "journal": {"title": "Addict Biol", "issn": "1369-1600", "volume": "24", "issue": "5", "pages": "935-945", "issn-l": "1355-6215"}, "abstract": "Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (Kp,uu,brain ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.", "doi": "10.1111/adb.12661", "pmid": "30088322", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-21T12:16:49.424Z", "modified": "2026-08-21T12:16:49.510Z"}