ArticleCellular signalling2017
Nalfurafine is a G-protein biased agonist having significantly greater bias at the human than rodent form of the kappa opioid receptor.
Article in Cellular signalling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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
80 citing papers in PubMed, 124 citations in OpenAlex.
- Kappa opioids suppress histaminergic itch by inhibiting mediodorsal thalamus-projecting claustrum glutamatergic neurons.Science advances · 2026Article
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- Mechanistic Insights into G Protein-Biased κ-Opioid Receptor Signaling Using Dual-Charged Naltrexamine Amides.Journal of medicinal chemistry · 2026Article
- Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A.Biomedicines · 2026Review
- Review
- G Protein Inactivation as a Mechanism for Addiction Treatment.Biological psychiatry · 2026Article
- Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025Article
- Structural and dynamic insights into the biased signaling mechanism of the human kappa opioid receptor.Nature communications · 2025Article
- KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder.Pharmacology, biochemistry, and behavior · 2025Review
- The role of RGS12 in tissue repair and human diseases.Genes & diseases · 2025Review
- Opioid Analgesics: Rise and Fall of Ligand Biased Signaling and Future Perspectives in the Quest for the Holy Grail.CNS drugs · 2025Review
- Pharmacological characterization of the novel selective kappa opioid receptor agonists 10-Iodo-Akuammicine and 10-Bromo-akuammicine in mice.Neuropharmacology · 2025Article
- Synchrony between midbrain gene transcription and dopamine terminal regulation is modulated by chronic alcohol drinking.Nature communications · 2025Article
- Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.Journal of medicinal chemistry · 2024Article
- Naltrexone blocks alcohol-induced effects on kappa-opioid receptors in the plasma membrane.Translational psychiatry · 2024Article
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Synthesis and evaluation of 3,4,5-trisubstituted triazoles as G protein-biased kappa opioid receptor agonists.European journal of medicinal chemistry · 2024Article
- Human IPSC-Derived PreBötC-Like Neurons and Development of an Opiate Overdose and Recovery Model.Advanced biology · 2024Article
- Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.Journal of medicinal chemistry · 2024Article
- Ultra-fast genetically encoded sensor for precise real-time monitoring of physiological and pathophysiological peroxide dynamics.Research square · 2024Article
20 more citing papers are in PubMed but not listed here.
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
Nalfurafine is a moderately selective kappa opioid receptor (KOR) analgesic with low incidence of dysphoric side effects in clinical development for the treatment of uremic pruritis. The basis for its reduced dysphoric effect compared to other KOR agonists is not clear, but prior studies suggest that the aversive properties of KOR agonists require p38α MAPK activation through an arrestin-dependent mechanism. To determine whether nalfurafine is a functionally selective KOR agonist, we measured its potency to activate the G protein-dependent early phase of Extracellular Signal-Regulated Kinase (ERK1/2) phosphorylation and the arrestin-dependent late phase of p38 MAPK signaling. Nalfurafine was approximately 250 fold more potent for ERK1/2 activation as compared to p38 MAPK activation in human KOR (hKOR) expressing HEK293 cells, and approximately 20 fold more potent for ERK1/2 activation than p38 activation in rodent KOR (rKOR) expressing HEK293 cells. The 10-fold greater G-bias at the hKOR than rKOR was unexpected, however the G protein biased effect of nalfurafine is consistent with its reduced dysphoric effects in human and rodent models. Although nalfurafine is reported to have low receptor selectivity in radioligand binding assays, its antinociceptive effect was blocked by the selective KOR antagonist norbinaltorphimine. Nalfurafine pretreatment also resulted in a KOR-dependent and mu opioid receptor-independent reduction in scratching induced by 5'-GNTI. These findings suggest that nalfurafine is a functionally selective KOR agonist and that KOR agonists able to selectively activate G protein signaling without activating p38α MAPK may have therapeutic potential as non-dysphoric antipruritic analgesics.
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.