ArticleProceedings of the National Academy of Sciences of the United States of America2013
Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 151 citations in OpenAlex.
- Structure-guided allosteric modulation of the delta opioid receptor.Nature communications · 2026Article
- Molecular mechanism of allosteric modulation of opioid receptors.Signal transduction and targeted therapy · 2026Article
- Gestodene Accelerates Cutaneous Wound Healing via PAR1-Selective Positive Allosteric Modulation.International journal of molecular sciences · 2026Article
- Effects of the Mu Opioid Receptor Positive Allosteric Modulator BMS-986122 On Opioid Efficacy in Rat Neuropathic Pain States.bioRxiv : the preprint server for biology · 2026Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.Nature communications · 2026Article
- A mu-opioid receptor positive allosteric modulator provides opioid-sparing antinociception without enhancing opioid side effects.The Journal of pharmacology and experimental therapeutics · 2026Article
- Discovery and dynamic pharmacology of μ-opioid receptor positive allosteric modulators.bioRxiv : the preprint server for biology · 2026Article
- Structure-based design of an opioid receptor modulator for enhanced morphine analgesia.Science advances · 2026Article
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- An orally bioavailable MrgprX1-positive allosteric modulator alleviates certain neuropathic pain-related behaviors in humanized mice.Science translational medicine · 2025Article
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- Inflaming and Immune-Resolving: The Ambivalent Role of Eosinophils in Osteoarthritis.International journal of molecular sciences · 2025Review
- Effects of two structurally diverse positive allosteric modulators on signaling bias at the μ-opioid receptor.Molecular pharmacology · 2025Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the μ-opioid receptor.bioRxiv : the preprint server for biology · 2025Article
- Reduced GIRK expression in midbrain dopamine neurons during prolonged abstinence from fentanyl self-administration.Psychopharmacology · 2025Article
- Mu Opioid Receptor Positive Allosteric Modulator BMS-986122 Confers Agonist-Dependent G Protein Subtype Signaling Bias.Biochemistry · 2025Article
- Advances in the structural understanding of opioid allostery.Trends in pharmacological sciences · 2025Review
- Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors.Molecular pharmacology · 2024Article
- Identification of c[D-Trp-Phe-β-Ala-β-Ala], the First κ-Opioid Receptor-Specific Negative Allosteric Modulator.ACS pharmacology & translational science · 2024Article
- Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
μ-Opioid receptors are among the most studied G protein-coupled receptors because of the therapeutic value of agonists, such as morphine, that are used to treat chronic pain. However, these drugs have significant side effects, such as respiratory suppression, constipation, allodynia, tolerance, and dependence, as well as abuse potential. Efforts to fine tune pain control while alleviating the side effects of drugs, both physiological and psychological, have led to the development of a wide variety of structurally diverse agonist ligands for the μ-opioid receptor, as well as compounds that target κ- and δ-opioid receptors. In recent years, the identification of allosteric ligands for some G protein-coupled receptors has provided breakthroughs in obtaining receptor subtype-selectivity that can reduce the overall side effect profiles of a potential drug. However, positive allosteric modulators (PAMs) can also have the specific advantage of only modulating the activity of the receptor when the orthosteric agonist occupies the receptor, thus maintaining spatial and temporal control of receptor signaling in vivo. This second advantage of allosteric modulators may yield breakthroughs in opioid receptor research and could lead to drugs with improved side-effect profiles or fewer tolerance and dependence issues compared with orthosteric opioid receptor agonists. Here, we describe the discovery and characterization of μ-opioid receptor PAMs and silent allosteric modulators, identified from high-throughput screening using a β-arrestin-recruitment assay.
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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.