Oxidative metabolism as a modulator of kratom's biological actions
S Chakraborty, R Uprety, ST Slocum, T Irie… - Journal of medicinal …, 2021 - ACS Publications
S Chakraborty, R Uprety, ST Slocum, T Irie, V Le Rouzic, X Li, LL Wilson, B Scouller…
Journal of medicinal chemistry, 2021•ACS PublicationsThe leaves of Mitragyna speciosa (kratom), a plant native to Southeast Asia, are increasingly
used as a pain reliever and for attenuation of opioid withdrawal symptoms. Using the tools of
natural products chemistry, chemical synthesis, and pharmacology, we provide a detailed in
vitro and in vivo pharmacological characterization of the alkaloids in kratom. We report that
metabolism of kratom's major alkaloid, mitragynine, in mice leads to formation of (a) a potent
mu opioid receptor agonist antinociceptive agent, 7-hydroxymitragynine, through a CYP3A …
used as a pain reliever and for attenuation of opioid withdrawal symptoms. Using the tools of
natural products chemistry, chemical synthesis, and pharmacology, we provide a detailed in
vitro and in vivo pharmacological characterization of the alkaloids in kratom. We report that
metabolism of kratom's major alkaloid, mitragynine, in mice leads to formation of (a) a potent
mu opioid receptor agonist antinociceptive agent, 7-hydroxymitragynine, through a CYP3A …
The leaves of Mitragyna speciosa (kratom), a plant native to Southeast Asia, are increasingly used as a pain reliever and for attenuation of opioid withdrawal symptoms. Using the tools of natural products chemistry, chemical synthesis, and pharmacology, we provide a detailed in vitro and in vivo pharmacological characterization of the alkaloids in kratom. We report that metabolism of kratom’s major alkaloid, mitragynine, in mice leads to formation of (a) a potent mu opioid receptor agonist antinociceptive agent, 7-hydroxymitragynine, through a CYP3A-mediated pathway, which exhibits reinforcing properties, inhibition of gastrointestinal (GI) transit and reduced hyperlocomotion, (b) a multifunctional mu agonist/delta-kappa antagonist, mitragynine pseudoindoxyl, through a CYP3A-mediated skeletal rearrangement, displaying reduced hyperlocomotion, inhibition of GI transit and reinforcing properties, and (c) a potentially toxic metabolite, 3-dehydromitragynine, through a non-CYP oxidation pathway. Our results indicate that the oxidative metabolism of the mitragynine template beyond 7-hydroxymitragynine may have implications in its overall pharmacology in vivo.
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