ArticleJournal of medicinal chemistry2016
Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 4 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
156 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Decoding kratom: molecular mechanisms and epigenetic factors in use and dependence.Translational psychiatry · 2026Pooled it
- Combining various acupuncture therapies with multimodal analgesia to enhance postoperative pain management following total knee arthroplasty: a network meta-analysis of randomized controlled trials.Frontiers in neurology · 2024Pooled it
- Qualitative content analysis of public responses to an FDA inquiry on the impact of scheduling changes to kratom.The International journal on drug policy · 2022Pooled it
- A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.Human psychopharmacology · 2022Pooled it
- Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder.Molecules (Basel, Switzerland) · 2024Trial
- Simultaneous quantification of seventeen kratom alkaloids and metabolites in human plasma and its application to clinical pharmacokinetic sample analysis.Pharmaceutical biology · 2026Article
- Discovery of putative G-protein-biased µ-opioid agonists via hierarchical virtual screening of ultra-large chemical space.Molecular diversity · 2026Article
- 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
- Kratom (Molecules (Basel, Switzerland) · 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
- Article
- Indole Alkaloids as Biased Opioid Receptor Modulators.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mixtures Biotransformation: Multilayer Molecular Networking of Kratom Liver Metabolites.Journal of natural products · 2026Article
- Discovery and dynamic pharmacology of μ-opioid receptor positive allosteric modulators.bioRxiv : the preprint server for biology · 2026Article
- Observational real-world analysis of dose-dependent effects ofFrontiers in pharmacology · 2026Article
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology. Herein, we report the pharmacology and SAR studies both in vitro and in vivo of mitragynine pseudoindoxyl (3), an oxidative rearrangement product of the corynanthe alkaloid mitragynine. 3 and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism/delta opioid receptor antagonism. In vitro, 3 and its analogs were potent agonists in [(35)S]GTPγS assays at the mu opioid receptor but failed to recruit β-arrestin-2, which is associated with opioid side effects. Additionally, 3 developed analgesic tolerance more slowly than morphine, showed limited physical dependence, respiratory depression, constipation, and displayed no reward or aversion in CPP/CPA assays, suggesting that analogs might represent a promising new generation of novel pain relievers.
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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.