Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
25 Dec 2023
25 Dec 2023
Historique:
received:
30
06
2023
accepted:
27
11
2023
revised:
20
11
2023
medline:
26
12
2023
pubmed:
26
12
2023
entrez:
25
12
2023
Statut:
aheadofprint
Résumé
(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
Identifiants
pubmed: 38145984
doi: 10.1038/s41380-023-02353-z
pii: 10.1038/s41380-023-02353-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Intramural NIH HHS
ID : ZIA DA000069
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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