Activity of Mitragyna speciosa ('Kratom') Alkaloids at Serotonin Receptors
| Autor: | Luis F. Restrepo, Erin C. Berthold, Aidan J. Hampson, Avi Patel, Lance R. McMahon, Carolina Lopera-Londoño, Takato Hiranita, Shyam H. Kamble, Samuel Obeng, Abhisheak Sharma, Lea R. Gamez-Jimenez, Francisco León, Clinton E. Canal, Marco Mottinelli, Christopher R. McCurdy, Yiming Chen, Tamara I. King |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Mitragyna speciosa Pharmacology Article Nociceptive Pain Rats Sprague-Dawley chemistry.chemical_compound In vivo Drug Discovery medicine Animals Humans 5-HT receptor Analgesics biology Behavior Animal Chemistry Alkaloid Antagonist biology.organism_classification Secologanin Tryptamine Alkaloids In vitro HEK293 Cells Opioid Mitragynine Receptors Serotonin Molecular Medicine Female medicine.drug |
| Zdroj: | J Med Chem |
| Popis: | 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-HT(1A)Rs and 5-HT(2B)Rs, unlike the principal kratom alkaloid mitragynine. Both alkaloids produced antinociceptive properties in rats via an opioid receptor-independent mechanism, and neither activated 5-HT(2B)Rs in vitro. Paynantheine, speciogynine, and mitragynine induced lower lip retraction and antinociception in rats, effects blocked by a selective 5-HT(1A)R antagonist. In vitro functional assays revealed that the in vivo 5-HT(1A)R 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-HT(2B)R, suggesting low inherent risk of causing valvulopathy. The 5-HT(1A)R agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use. |
| Databáze: | OpenAIRE |
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