| Literature DB >> 34467758 |
Francisco León1,2, Samuel Obeng1,3, Marco Mottinelli1, Yiming Chen4, Tamara I King5,6, Erin C Berthold5,6, Shyam H Kamble5,6, Luis F Restrepo3, Avi Patel3, Lea R Gamez-Jimenez3, Carolina Lopera-Londoño1, Takato Hiranita3, Abhisheak Sharma5,6, Aidan J Hampson7, Clinton E Canal4, Lance R McMahon3, Christopher R McCurdy1,6.
Abstract
Kratom alkaloids have mostly been evaluated for their opioid activity but less at other targets that could contribute to their physiological effects. Here, we investigated the in vitro and in vivo activity of kratom alkaloids at serotonin receptors (5-HTRs). Paynantheine and speciogynine exhibited high affinity for 5-HT1ARs and 5-HT2BRs, unlike the principal kratom alkaloid mitragynine. Both alkaloids produced antinociceptive properties in rats via an opioid receptor-independent mechanism, and neither activated 5-HT2BRs in vitro. Paynantheine, speciogynine, and mitragynine induced lower lip retraction and antinociception in rats, effects blocked by a selective 5-HT1AR antagonist. In vitro functional assays revealed that the in vivo 5-HT1AR agonistic effects may be due to the metabolites 9-O-desmethylspeciogynine and 9-O-desmethylpaynantheine and not the parent compounds. Both metabolites did not activate 5-HT2BR, suggesting low inherent risk of causing valvulopathy. The 5-HT1AR agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use.Entities:
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Year: 2021 PMID： 34467758 PMCID： PMC9235362 DOI： 10.1021/acs.jmedchem.1c00726
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 8.039