ReviewPharmacological research2022
An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.
Review in Pharmacological research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 26 citations in OpenAlex.
- Impact of oliceridine versus sufentanil on postoperative nausea and vomiting in patients undergoing thyroid surgery: a prospective, double-blind, randomized controlled trial.Annals of medicine · 2026Trial
- Rational design of a Kappa opioid receptor peptide agonist with attenuated β-arrestin signaling.Nature communications · 2026Article
- Effect of oliceridine on hypoxia during sedated hysteroscopy: a Phase 4 randomized clinical trial.Communications medicine · 2026Article
- Review
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- Depression of intracranial self-stimulation in male and female rats by intraperitoneal lactic acid: effects of morphine, ketoprofen, and interactions with G-protein biased kappa opioid agonists.Psychopharmacology · 2025Article
- Effects of Biased Analogues of the Kappa Opioid Receptor Agonist, U50,488, in Preclinical Models of Pain and Side Effects.Molecules (Basel, Switzerland) · 2025Article
- Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.Journal of medicinal chemistry · 2024Article
- In Vitro and In Vivo Pharmacological Profiles of LENART01, a Dermorphin-Ranatensin Hybrid Peptide.International journal of molecular sciences · 2024Article
- κ-Opioid receptor activation attenuates osteoarthritis synovitis by regulating macrophage polarization through the NF-κB pathway.Acta biochimica et biophysica Sinica · 2024Article
- Review
- Bifunctional Peptidomimetic G Protein-Biased Mu-Opioid Receptor Agonist and Neuropeptide FF Receptor Antagonist KGFF09 Shows Efficacy in Visceral Pain without Rewarding Effects after Subcutaneous Administration in Mice.Molecules (Basel, Switzerland) · 2022Article
- Opioids and Their Receptors: Present and Emerging Concepts in Opioid Drug Discovery II.Molecules (Basel, Switzerland) · 2022Article
- Quantitative Systems Pharmacology and Biased Agonism at Opioid Receptors: A Potential Avenue for Improved Analgesics.International journal of molecular sciences · 2022Review
- Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.Pharmacology, biochemistry, and behavior · 2022Article
- Pharmacology of Kappa Opioid Receptors: Novel Assays and Ligands.Frontiers in pharmacology · 2022Article
- Signaling underlying kappa opioid receptor-mediated behaviors in rodents.Frontiers in neuroscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Kappa opioid receptor (κOR) agonists lack the abuse liability and respiratory depression effects of clinically used mu opioid receptor (μOR) analgesics and are hypothesized to be safer alternatives. However, κOR agonists have limiting adverse effects of their own, including aversion, sedation, and mood effects, that have hampered their clinical translation. Studies performed over the last 15 years have suggested that these adverse effects could result from activation of distinct intracellular signaling pathways that are dependent on β-arrestin, whereas signaling downstream of G protein activation produces antinociception. This led to the hypothesis that agonists biased away from β-arrestin signaling would have improved therapeutic windows over traditional unbiased agonists and allow for clinical development of analgesic G-protein-biased κOR agonists. Given a recent controversy regarding the benefits of G-protein-biased μOR agonists, it is timely to reassess the therapeutic promise of G-protein-biased κOR agonists. Here we review recent discoveries from preclinical κOR studies and critically evaluate the therapeutic windows of G-protein-biased κOR agonists in each of the adverse effects above. Overall, we find that G-protein-biased κOR agonists generally have improved therapeutic window relative to unbiased agonists, although frequently study design limits strong conclusions in this regard. However, a steady flow of newly developed biased κOR agonists paired with recently engineered behavioral and molecular tools puts the κOR field in a prime position to make major advances in our understanding of κOR function and fulfill the promise of translating a new generation of biased κOR agonists to the clinic.
Indexed as
Identifiers
What Socratic 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 Socratic graph.