ArticleBritish journal of pharmacology2020
Morphine-induced respiratory depression is independent of β-arrestin2 signalling.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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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
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.
- Pooled it
- Tegileridine, a Biased μ-Opioid Receptor Agonist, versus Oxycodone for Postoperative Analgesia and Postoperative Nausea and Vomiting After Total Laparoscopic Hysterectomy: A Randomized, Double-Blind, Single-Center, Controlled Trial.Drug design, development and therapy · 2026Trial
- Internet Sales of "Research Grade Compounds": The Opioid SR-17018 (SR-17) as an Example.Cureus · 2026Review
- Data Analysis Planning and Reporting for Confirmatory Multi-Lab Preclinical Trials: A Tutorial.Biometrical journal. Biometrische Zeitschrift · 2026Review
- Dynamic Pathway Selectivity of TAS2R5 toward or Away from β-Arrestin or G Protein from Biased Agonists.Biochemistry · 2026Article
- Structure-Activity Relationships and Ligand-Dependent Arrestin Bias in μ-Opioid Receptor-Mediated ERK Activation.Biomolecules & therapeutics · 2026Article
- Divergence in μ and δ opioid receptor pharmacology in neurons and antinociceptive efficacy in neuropathic pain: Insights from MP135 and CYM51010.British journal of pharmacology · 2026Article
- Rational design of a Kappa opioid receptor peptide agonist with attenuated β-arrestin signaling.Nature communications · 2026Article
- Knowledge graph and emerging trends in β-arrestin research on pain: a bibliometric analysis (1997-2025).Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A comprehensive review on pain: Model, target, therapy, and prospect (Review).International journal of molecular medicine · 2026Review
- Biased Signaling in Psychedelic Action.Annual review of pharmacology and toxicology · 2026Review
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- The Role of Danavorexton for Perioperative Opioid-Induced Respiratory Depression and Sedation: A Narrative Review.Clinical pharmacology : advances and applications · 2026Review
- Autonomic nervous system modulation by G protein-biased mu-opioid receptor agonists: A translational scoping review protocol.PloS one · 2026Article
- Quantum Chemical Exploration of Fentanyl and Its Analogs: Conformational Landscapes and Energetics in Solution.ACS omega · 2025Article
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Mitragynine and 7-hydroxymitragynine: Bidirectional effects on breathing in rats.The Journal of pharmacology and experimental therapeutics · 2025Article
- Rational Design Biased Compounds against μ‑Opioid Receptor.ACS pharmacology & translational science · 2025Article
- Total synthesis and biological activity of "carbamorphine": O-to-CHProceedings of the National Academy of Sciences of the United States of America · 2025Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
background and purposeGPCRs can signal through both G proteins and β-arrestin2. For the μ-opioid receptor, early experimental evidence from a single study suggested that G protein signalling mediates analgesia, whereas β-arrestin2 signalling mediates respiratory depression and constipation. Consequently, for more than a decade, much research effort has been focused on developing biased μ-opioid agonists that preferentially target G protein signalling over β-arrestin signalling, as it was believed that such drugs would be analgesics devoid of respiratory depressant activity. However, the prototypical compounds that have been developed based on this concept have so far failed in clinical and preclinical development. EXPERIMENTAL APPROACH: The present study was set up to re-examine opioid-induced respiratory depression in β-arrestin2 knockout mice. To this end, a consortium was formed consisting of three different laboratories located in different countries to evaluate independently opioid-induced respiratory depression. KEY
resultsOur consensus results unequivocally demonstrate that the prototypical μ-opioid agonist morphine (3.75-100 mg·kg CONCLUSION AND IMPLICATIONS: Our findings do not support the original suggestion that β-arrestin2 signalling plays a key role in opioid-induced respiratory depression and call into question the concept of developing G protein-biased μ-opioid receptor agonists as a strategy for the development of safer opioid analgesic drugs.
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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.