ArticlePsychopharmacology2015
The opioid receptor pharmacology of GSK1521498 compared to other ligands with differential effects on compulsive reward-related behaviours.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Opioid Antagonists and the A118G Polymorphism in the μ-Opioid Receptor Gene: Effects of GSK1521498 and Naltrexone in Healthy Drinkers Stratified by OPRM1 Genotype.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Trial
- Nalmefene and naltrexone reduce alcohol intake via selective efficacy in subpopulations distinguished by behavioral and blood-based biomarkers.Communications medicine · 2026Article
- Total-body imaging of mu-opioid receptors with [European journal of nuclear medicine and molecular imaging · 2024Article
- The Oxford Catalogue of Opioids: A systematic synthesis of opioid drug names and their pharmacology.British journal of clinical pharmacology · 2021Article
- Lessons learned from using fMRI in the early clinical development of a mu-opioid receptor antagonist for disorders of compulsive consumption.Psychopharmacology · 2021Review
- National Institutes of Health (NIH) Executive Meeting Summary: Developing Medical Countermeasures to Rescue Opioid-Induced Respiratory Depression (a Trans-Agency Scientific Meeting)-August 6/7, 2019.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2020Article
- Design and synthesis of a bivalent probe targeting the putative mu opioid receptor and chemokine receptor CXCR4 heterodimer.RSC medicinal chemistry · 2020Article
- Antidepressant-like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice.British journal of pharmacology · 2018Article
- Evidence for a Long-Lasting Compulsive Alcohol Seeking Phenotype in Rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Obesity: Current and potential pharmacotherapeutics and targets.Pharmacology & therapeutics · 2017Review
- The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.Psychopharmacology · 2015Article
- Response to paper by Kelly et al "The opioid receptor pharmacology of GSK1521498 compared to other ligands with different effects on compulsive reward-related behaviors" published in Psychopharmacology 232, 305-314, 2014.Psychopharmacology · 2015Article
- Reply to Wang and Sadée.Psychopharmacology · 2015Article
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9 authors at 4 institutions in 2 countries.
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Abstract
rationaleThe novel opioid receptor antagonist, GSK1421498, has been shown to attenuate reward-driven compulsive behaviours, such as stimulant drug seeking or binge eating, in animals and humans. Here, we report new data on the receptor pharmacology of GSK121498, in comparison to naltrexone, naloxone, 6-β-naltrexol and nalmefene.
objectivesTo determine whether the novel opioid antagonist, GSK1521498, is an orthosteric or allosteric antagonist at the μ opioid receptor (MOPr) and whether it has neutral antagonist or inverse agonist properties.
methodsA combination of radioligand binding assays and [(35)S]GTPγS binding assays was employed.
resultsGSK1521498 completely displaced [(3)H]naloxone binding to MOPr and did not alter the rate of [(3)H]naloxone dissociation from MOPr observations compatible with it binding to the orthosteric site on MOPr. GSK1521498 exhibited inverse agonism when MOPr was overexpressed but not when the level of MOPr expression was low. In parallel studies under conditions of high receptor expression density, naloxone, naltrexone, 6-β-naltrexol and nalmefene exhibited partial agonism, not inverse agonism as has been reported previously for naloxone and naltrexone. In brain tissue from mice receiving a prolonged morphine pre-treatment, GSK1521498 exhibited slight inverse agonism.
conclusionsDifferences between GSK1521498 and naltrexone in their effects on compulsive reward seeking are arguably linked to the more selective and complete MOPr antagonism of GSK1521498 versus the partial MOPr agonism of naltrexone. GSK1521498 is also pharmacologically differentiated by its inverse agonist efficacy at high levels of MOPr expression, but this may be less likely to contribute to behavioural differentiation at patho-physiological levels of expression.
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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.