The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
07 06 2023
07 06 2023
Historique:
received:
14
03
2023
accepted:
12
05
2023
revised:
02
05
2023
medline:
9
6
2023
pubmed:
8
6
2023
entrez:
7
6
2023
Statut:
epublish
Résumé
Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (E
Identifiants
pubmed: 37286536
doi: 10.1038/s41398-023-02473-8
pii: 10.1038/s41398-023-02473-8
pmc: PMC10247777
doi:
Substances chimiques
Oxycodone
CD35PMG570
Receptors, N-Methyl-D-Aspartate
0
Dextromethorphan
7355X3ROTS
Ketamine
690G0D6V8H
Analgesics, Opioid
0
Illicit Drugs
0
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
192Informations de copyright
© 2023. The Author(s).
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