ArticleNaunyn-Schmiedeberg's archives of pharmacology2019
The inhibitory effects of mitragynine on P-glycoprotein in vitro.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- Evaluating the drug interactions in kratom usage: clinical application.Expert opinion on drug metabolism & toxicology · 2025Review
- Structure-based discovery of novel P-glycoprotein inhibitors targeting the nucleotide binding domains.Scientific reports · 2023Article
- A Critical Review of the Neuropharmacological Effects of Kratom: An Insight from the Functional Array of Identified Natural Compounds.Molecules (Basel, Switzerland) · 2023Review
- Translating Kratom-Drug Interactions: From Bedside to Bench and Back.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Developing a Knowledge Graph for Pharmacokinetic Natural Product-Drug Interactions.Journal of biomedical informatics · 2023Article
- Understanding Kratom Use: A Guide for Healthcare Providers.Frontiers in pharmacology · 2022Review
- Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers.Frontiers in pharmacology · 2021Review
- A New Data Repository for Pharmacokinetic Natural Product-Drug Interactions: From Chemical Characterization to Clinical Studies.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- The Potential for Kratom as an Antidepressant and Antipsychotic.The Yale journal of biology and medicine · 2020Review
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Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.