Open AccessMetabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy
Author(s) -
Shyam H. Kamble,
Francisco León,
Tamara I. King,
Erin C. Berthold,
Carolina Lopera-Londoño,
K. Kanaka Raju,
Aidan Hampson,
Abhisheak Sharma,
Bonnie A. Avery,
Lance Richard McMahon,
Christopher R. McCurdy
Publication year - 2020
Publication title -
acs pharmacology and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.271
H-Index - 10
ISSN - 2575-9108
DOI - 10.1021/acsptsci.0c00075
Subject(s) - metabolite , alkaloid , pharmacology , opioid , potency , opioid receptor , chemistry , agonist , biology , receptor , in vitro , biochemistry , stereochemistry
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.