ArticleJournal of the American Chemical Society2016
Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07713771 (Effectiveness of Mitragynine Topical Patch From Kratom for Pain Reduction in Myofascial Pain Syndrome of Upper Trapezius Muscle), which is not on this map. Cited by 146 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effectiveness of Mitragynine Topical Patch From Kratom for Pain Reduction in Myofascial Pain Syndrome of Upper Trapezius Muscle: Double Blinded Placebo, Randomized Controlled Trial
Who cites it
146 citing papers in PubMed, 2 syntheses or guidelines pooled it, 302 citations in OpenAlex.
- Decoding kratom: molecular mechanisms and epigenetic factors in use and dependence.Translational psychiatry · 2026Pooled it
- A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.Human psychopharmacology · 2022Pooled it
- Assessment of Abuse Potential-Related Effects of Oral Dried Kratom Leaf Powder in Healthy Normal Participants Following Single and Multiple Daily Doses.Drug testing and analysis · 2026Trial
- Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder.Molecules (Basel, Switzerland) · 2024Trial
- Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study.The Yale journal of biology and medicine · 2020Trial
- Integrated quantitative proteomics reveals stress-associated network remodeling induced by mitragynine in RSC96 Schwann cells.Archives of toxicology · 2026Article
- Kratom Toxicity: Pharmacologic Mechanisms, Clinical Risks, and Management Considerations.Cureus · 2026Review
- Mitragynine and 7-hydroxy-mitragyine plasma pharmacokinetics in humans after single and 15 multiple oral kratom extract doses.Journal of analytical toxicology · 2026Article
- A review on Mitragyna alkaloids pharmacology, biosynthesis and biotechnological insights.Journal, genetic engineering & biotechnology · 2026Review
- Atypical respiration patterns of kratom alkaloids.The Journal of pharmacology and experimental therapeutics · 2026Article
- Mitragynine and Morphine Stabilize Different Conformations of the μ‑Opioid Receptor as Revealed by Molecular Dynamics Simulation Studies.ACS omega · 2026Article
- Investigating Opioid Receptor Activity through Biocatalytic Halogenation and Oxidation of Mitragynine.ACS chemical biology · 2026Article
- Mapping partial agonism of mitragynine at the µ-opioid receptor through molecular dynamics and Markov state modelling analysis.Scientific reports · 2026Article
- Exploratory evaluation of encapsulated kratom using multimodal quantitative sensory testing in dogs.Frontiers in pharmacology · 2026Article
- UV-B and far-red light shape morphological and phytochemical responses in kratom.Frontiers in plant science · 2026Article
- Observational real-world analysis of dose-dependent effects ofFrontiers in pharmacology · 2026Article
- A Review of Kratom Product Evolution and Its Associated Health Outcomes.Substance abuse and rehabilitation · 2026Review
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- In Vitro Pharmacology of Mitragynine at α-Adrenoceptors.ACS chemical neuroscience · 2025Article
- From kratom to 7-hydroxymitragynine: evolution of a natural remedy into a public-health threat.Pharmaceutical biology · 2025Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.
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What OpenQuestion holds
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.