ReviewBritish journal of pharmacology2012
Ligand-directed signalling within the opioid receptor family.
Review in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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
71 citing papers in PubMed, 143 citations in OpenAlex.
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?The American journal of psychiatry · 2025Review
- Synthesis and biochemical evaluation of 17-N-beta-aminoalkyl-4,5α-epoxynormorphinans.Scientific reports · 2023Article
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- State and Future Science of Opioids and Potential of Biased-ligand Technology in the Management of Acute Pain After Burn Injury.Journal of burn care & research : official publication of the American Burn Association · 2023Review
- Quantitative Systems Pharmacology and Biased Agonism at Opioid Receptors: A Potential Avenue for Improved Analgesics.International journal of molecular sciences · 2022Review
- Fundamentals of the Dynorphins/Kappa Opioid Receptor System: From Distribution to Signaling and Function.Handbook of experimental pharmacology · 2022Article
- In Silico Identification of Tripeptides as Lead Compounds for the Design of KOR Ligands.Molecules (Basel, Switzerland) · 2021Article
- LP1 and LP2: Dual-Target MOPr/DOPr Ligands as Drug Candidates for Persistent Pain Relief.Molecules (Basel, Switzerland) · 2021Review
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Natural Products for the Treatment of Pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide.Biochemistry · 2021Review
- Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.eLife · 2021Article
- Recent advances in basic science methodology to evaluate opioid safety profiles and to understand opioid activities.Faculty reviews · 2021Review
- A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia.Headache · 2021Article
- Chemical syntheses of the salvinorin chemotype of KOR agonist.Natural product reports · 2020Review
- Pain, Motivation, Migraine, and the Microbiome: New Frontiers for Opioid Systems and Disease.Molecular pharmacology · 2020Review
- Spinal Opioid Tolerance Depends upon Platelet-Derived Growth Factor Receptor-Molecular pharmacology · 2020Article
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- Endogenous Opioids at the Intersection of Opioid Addiction, Pain, and Depression: The Search for a Precision Medicine Approach.Annual review of neuroscience · 2020Review
- Biased signaling by endogenous opioid peptides.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
11 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 3 institutions in 2 countries.
Funding
Abstract
The classic model of GPCR activation proposed that all agonists induce the same active receptor conformation. However, research over the last decade has shown that GPCRs exist in multiple conformations, and that agonists can stabilize different active states. The distinct receptor conformations induced by ligands result in distinct receptor-effector complexes, which produce varying levels of activation or inhibition of subsequent signalling cascades. This concept, referred to as ligand-directed signalling or biased agonism has important biological and therapeutic implications. Opioid receptors are G(i/o) GPCRs and regulate a number of important physiological functions, including pain, reward, mood, stress, gastrointestinal transport and respiration. A number of in vitro studies have shown biased agonism at the three opioid receptors (µ, δ and κ); however, in vivo consequences of this phenomenon have only recently been demonstrated. For the µ and δ opioid receptors, the majority of reported ligand selective behavioural effects are observed as differential adaptations to repeated drug administration. In terms of the κ opioid receptor, clear links between ligand-selective signalling events and specific in vivo responses have been recently characterized. Drugs for all three receptors are either already used or are being developed for clinical applications. There is clearly a need to better characterize the specific events that occur following agonist stimulation and how these relate to in vivo responses. This understanding could eventually lead to the development of tailor-made pharmacotherapies where advantageous drug effects can be selectively targeted over adverse effects.
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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.