ArticleeLife2021
ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Internet Sales of "Research Grade Compounds": The Opioid SR-17018 (SR-17) as an Example.Cureus · 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
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- Structure-Bias Relationship of μ-Opioid Receptor Agonists.Handbook of experimental pharmacology · 2026Review
- Quantum Chemical Exploration of Fentanyl and Its Analogs: Conformational Landscapes and Energetics in Solution.ACS omega · 2025Article
- 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
- Semi-synthesis in the exploration of opioid-targeting natural products.Natural product reports · 2025Review
- Expanding Horizons of Buprenorphine: A Comprehensive Narrative Review of Its Pharmacological Properties and Clinical Applications in Chronic Pain.Pain and therapy · 2025Review
- Profiling the proximal proteome of the activated μ-opioid receptor.Nature chemical biology · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Article
- In Vitro Functional Profiling of Fentanyl and Nitazene Analogs at the μ-Opioid Receptor Reveals High Efficacy for Gi Protein Signaling.ACS chemical neuroscience · 2024Article
- A Balancing Act: Learning from the Past to Build a Future-Focused Opioid Strategy.Annual review of physiology · 2024Review
- Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor.Nature communications · 2023Article
- Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.British journal of pharmacology · 2023Article
- Review
- Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine DJournal of medicinal chemistry · 2023Article
- Article
- Heroin and its metabolites: relevance to heroin use disorder.Translational psychiatry · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Opioids are perhaps the most effective analgesics in medicine. However, between 1999 and 2018, over 400,000 people in the United States died from opioid overdose. Excessive opioids make breathing lethally slow and shallow, a side-effect called opioid-induced respiratory depression. This doubled-edged sword has sparked the desire to develop novel therapeutics that provide opioid-like analgesia without depressing breathing. One such approach has been the design of so-called 'biased agonists' that signal through some, but not all pathways downstream of the µ-opioid receptor (MOR), the target of morphine and other opioid analgesics. This rationale stems from a study suggesting that MOR-induced ß-arrestin 2 dependent signaling is responsible for opioid respiratory depression, whereas adenylyl cyclase inhibition produces analgesia. To verify this important result that motivated the 'biased agonist' approach, we re-examined breathing in ß-arrestin 2-deficient mice and instead find no connection between ß-arrestin 2 and opioid respiratory depression. This result suggests that any attenuated effect of 'biased agonists' on breathing is through an as-yet defined mechanism.
Indexed as
Identifiers
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.