ArticleProceedings of the National Academy of Sciences of the United States of America2021
G protein signaling-biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07372209 (Study of Effects and Underlying Mechanisms of Analgesic Drugs on Inflammatory Pathways and Immune Function in Patients With Endometrial Cancer), which is not on this map. Cited by 16 papers.
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.
Study of Effects and Underlying Mechanisms of Analgesic Drugs on Inflammatory Pathways and Immune Function in Patients With Endometrial Cancer
Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Characterization of the GTPγS release function of a G protein-coupled receptor.Nature communications · 2025Article
- Pharmacology and Toxicology of Opioids-Recent Advances and New Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- Exploring the constitutive activation mechanism of the class A orphan GPR20.Acta pharmacologica Sinica · 2025Article
- Insurmountable antagonism of human mu opioid receptors by buprenorphine is due to hemi-equilibrium.European journal of pharmacology · 2025Article
- GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.British journal of pharmacology · 2023Article
- Article
- Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine.Biomolecules · 2023Article
- New paradigms in purinergic receptor ligand discovery.Neuropharmacology · 2023Review
- Essential role of P-glycoprotein in the mechanism of action of oliceridine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- A Journey through Diastereomeric Space: The Design, Synthesis, In Vitro and In Vivo Pharmacological Activity, and Molecular Modeling of Novel Potent Diastereomeric MOR Agonists and Antagonists.Molecules (Basel, Switzerland) · 2022Article
- Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk.Antioxidants (Basel, Switzerland) · 2022Review
- MRAP2 inhibits β-arrestin recruitment to the ghrelin receptor by preventing GHSR1a phosphorylation.The Journal of biological chemistry · 2022Article
- Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The ability of a ligand to preferentially promote engagement of one signaling pathway over another downstream of GPCR activation has been referred to as signaling bias, functional selectivity, and biased agonism. The presentation of ligand bias reflects selectivity between active states of the receptor, which may result in the display of preferential engagement with one signaling pathway over another. In this study, we provide evidence that the G protein-biased mu opioid receptor (MOR) agonists SR-17018 and SR-14968 stabilize the MOR in a wash-resistant yet antagonist-reversible G protein-signaling state. Furthermore, we demonstrate that these structurally related biased agonists are noncompetitive for radiolabeled MOR antagonist binding, and while they stimulate G protein signaling in mouse brains, partial agonists of this class do not compete with full agonist activation. Importantly, opioid antagonists can readily reverse their effects in vivo. Given that chronic treatment with SR-17018 does not lead to tolerance in several mouse pain models, this feature may be desirable for the development of long-lasting opioid analgesics that remain sensitive to antagonist reversal of respiratory suppression.
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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.