Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy.
ACS Pharmacol Transl Sci
; 3(6): 1063-1068, 2020 Dec 11.
Article
in En
| MEDLINE
| ID: mdl-33344889
ABSTRACT
Kratom is widely consumed in the United States for self-treatment of pain and opioid withdrawal symptoms. Mitragynine is the most abundant alkaloid in kratom and is a µ-opioid receptor agonist. 7-Hydroxymitragynine (7-HMG) is a mitragynine metabolite that is a more potent and efficacious opioid than its parent mitragynine. 7-HMG contributes to mitragynine's antinociceptive effects in mice, but evidence suggests it may also have a higher abuse potential. This in vitro study demonstrates that 7-HMG is stable in rodent and monkey plasma but is unstable in human plasma. Surprisingly, in human plasma 7-HMG is converted to mitragynine pseudoindoxyl, an opioid that is even more potent than either mitragynine or 7-HMG. This novel metabolite is formed in human plasma to a much greater extent than in the preclinical species tested (mouse, rat, dog, and cynomolgus monkey) and due to its µ-opioid potency may substantially contribute to the pharmacology of kratom in humans to a greater extent than in other tested species.
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Pharmacol Transl Sci
Year:
2020
Document type:
Article
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