ArticleMolecular psychiatry2024
Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone.
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Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15citing papers in PubMed
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Who cites it
15 citing papers in PubMed.
- The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.Translational psychiatry · 2023Trial
- Dopaminergic hypersensitivity of the opioid-responsive striatal-entopeduncular pathway in a rodent model of restless legs syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Emerging Insights into the Distinct Pharmacological Mechanisms of Buprenorphine.Journal of chemical information and modeling · 2026Article
- Article
- Levomethadone Selectively Reduces Emotional Impulsivity in ASRS-Positive ADHD-OUD Patients, Independent of Dose Escalation.Journal of clinical medicine · 2025Article
- Methadone and morphine have equivalent analgesic but not reward potency in female mice.Addiction neuroscience · 2025Article
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- Circuit-selective pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.Cell reports · 2025Article
- Subcutaneous methadone is not different than transdermal fentanyl for postoperative analgesia in dogs with thoracolumbar disc disease, a prospective, randomised, blinded clinical study.BMC veterinary research · 2025Article
- Distinctive biochemical properties of the μ-opioid receptor-corticotropin- releasing factor CRFPharmacological research · 2025Article
- Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.CNS spectrums · 2025Review
- New Synthesis and Pharmacological Evaluation of Enantiomerically Pure (Journal of medicinal chemistry · 2025Article
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?The American journal of psychiatry · 2025Review
- Mixed-mechanism analgesics for mixed pain.Frontiers in medicine · 2025Article
- Letter to the Editor regarding 'Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone'.Molecular psychiatry · 2024Article
Corrections and comments
- Update of
Authors and funding
20 authors.
Marjorie R Levinstein *Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.ORCID 0000-0003-4360-1503
Paulo A De Oliveira *Integrative Neurobiology Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
Nil Casajuana-Martin *Laboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Barcelona, Spain.ORCID 0000-0002-9007-274X
Cesar QuirozIntegrative Neurobiology Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
Reece C BudinichBiobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
Rana RaisJohns Hopkins Drug Discovery, Neurology and Pharmacology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
William ReaIntegrative Neurobiology Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
Emilya N VentrigliaBiobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
Natàlia LlopartLaboratory of Molecular Neuropharmacology, Department of Biochemistry and Molecular Biomedicine, Faculty of Biology and Institut de Biomedicina de la Universitat de Barcelona, 08028, Barcelona, Spain.ORCID 0000-0002-3127-2901
Verònica Casadó-AngueraLaboratory of Molecular Neuropharmacology, Department of Biochemistry and Molecular Biomedicine, Faculty of Biology and Institut de Biomedicina de la Universitat de Barcelona, 08028, Barcelona, Spain.
Estefanía MorenoLaboratory of Molecular Neuropharmacology, Department of Biochemistry and Molecular Biomedicine, Faculty of Biology and Institut de Biomedicina de la Universitat de Barcelona, 08028, Barcelona, Spain.ORCID 0000-0002-2491-5753
Donna WaltherDesigner Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
Grant C GlatfelterDesigner Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
David WeinshenkerDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.ORCID 0000-0002-3678-6215
Carlos A ZarateSection on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health Intramural Research Program, Bethesda, MD, 20892, USA.
Vicent CasadóLaboratory of Molecular Neuropharmacology, Department of Biochemistry and Molecular Biomedicine, Faculty of Biology and Institut de Biomedicina de la Universitat de Barcelona, 08028, Barcelona, Spain.ORCID 0000-0002-1764-3825
Michael H BaumannDesigner Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
Leonardo PardoLaboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Universitat Autònoma Barcelona, Bellaterra, 08193, Barcelona, Spain.
Sergi FerréIntegrative Neurobiology Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA. sergi.ferre@nih.gov.ORCID 0000-0002-1747-1779
Michael MichaelidesBiobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA. mike.michaelides@nih.gov.ORCID 0000-0003-0398-4917
Funding
Neurotransmitter Receptor Heteromers in the Striatal Spine ModuleZIADA000493 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI FERRE, SERGI · 2009 to 2025
$35.6MBiobehavioral Imaging and Molecular Neuropsychopharmacology of Substance Abuse MechanismsZIADA000069 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI MICHAELIDES, MICHAEL · 2016 to 2025
$18.9MPreclinical medication development for stimulant use disorderZIADA000522 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI BAUMANN, MICHAEL · 2009 to 2025
$8.9MContribution of locus coeruleus-derived galanin to opioid reward and reinforcementR01DA049257 · NIDA · EMORY UNIVERSITY · PI WEINSHENKER, DAVID · 2020 to 2024
$2.3MGeneralitat de Catalunya (Government of Catalonia) 2021-SGR-00230Intramural NIH HHS ZIA DA000069Intramural NIH HHS ZIA DA000493Intramural NIH HHS ZIA DA000522Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación) Juan de la Cierva fellowship FJC2019-041020-IMinistry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación) PID2020-113938RB-I00Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación) PID2022-140912OB-I00NIDA NIH HHS R01 DA049257U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA049257U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) ZIA000522
Abstract
(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. We compared the pharmacology of (R)-MTD and (S)-MTD and found they bind to MORs, but not NMDARs, and induce full analgesia. Unlike (R)-MTD, (S)-MTD was a weak reinforcer that failed to affect extracellular dopamine or induce locomotor stimulation. Furthermore, (S)-MTD antagonized motor and dopamine releasing effects of (R)-MTD. (S)-MTD acted as a partial agonist at MOR, with complete loss of efficacy at the MOR-galanin Gal
Indexed as
Analgesics, OpioidMethadoneReceptors, Opioid, muAnimalsDopamineHumansLigandsMaleMiceReceptors, N-Methyl-D-AspartateStereoisomerismAnalgesics, OpioidDopamineLigandsMethadoneReceptors, N-Methyl-D-AspartateReceptors, Opioid, mu
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