Dextromethadone: Difference between revisions
| [unchecked revision] | [unchecked revision] |
Create Dextromethadone page (Stahl-sourced detail with skepticism) |
Sentence-case category link per house style (NMDA_Receptor_Antagonists → NMDA_receptor_antagonists) |
||
| (One intermediate revision by one other user not shown) | |||
| Line 15: | Line 15: | ||
| legal = Investigational | | legal = Investigational | ||
| intro = '''Dextromethadone''' (also known as esmethadone or REL-1017) is the dextro-enantiomer of methadone, currently in clinical development as a rapid-onset oral antidepressant. Unlike levo-methadone (the opioid-active enantiomer used in opioid agonist therapy), dextromethadone is a relatively selective NMDA receptor antagonist with low channel-trapping properties and minimal μ-opioid activity. The development hypothesis is that targeting NMDA receptors can produce rapid antidepressant response (like ketamine/esketamine/Auvelity) without the dissociative and abuse-liability profile of ketamine. Phase 3 results have been mixed; FDA approval status uncertain as of mid-2024. | | intro = '''Dextromethadone''' (also known as esmethadone or REL-1017) is the dextro-enantiomer of methadone, currently in clinical development as a rapid-onset oral antidepressant. Unlike levo-methadone (the opioid-active enantiomer used in opioid agonist therapy), dextromethadone is a relatively selective NMDA receptor antagonist with low channel-trapping properties and minimal μ-opioid activity. The development hypothesis is that targeting NMDA receptors can produce rapid antidepressant response (like ketamine/esketamine/Auvelity) without the dissociative and abuse-liability profile of ketamine. Phase 3 results have been mixed; FDA approval status uncertain as of mid-2024. | ||
| pharmacodynamics= Uncompetitive NMDA receptor antagonist with low channel-trapping (binds open channel briefly, then dissociates | | pharmacodynamics= Uncompetitive NMDA receptor antagonist with low channel-trapping (binds open channel briefly, then dissociates, less than ketamine's high-trapping). Weak μ-opioid agonist (~30-fold less than levomethadone). Some 5HT2A and sigma-1 binding. | ||
| effects = In trials: generally well-tolerated. Headache, dizziness, nausea reported. Less dissociation than ketamine. | | effects = In trials: generally well-tolerated. Headache, dizziness, nausea reported. Less dissociation than ketamine. | ||
| interactions = <pharmaInteractions/> | | interactions = <pharmaInteractions/> | ||
}} | }} | ||
[[Category:NMDA | [[Category:NMDA receptor antagonists]] | ||
[[Category:Antidepressants]] | [[Category:Antidepressants]] | ||
[[Category:Dissociatives]] | [[Category:Dissociatives]] | ||
Latest revision as of 05:02, 23 May 2026
NMDA receptor antagonist (uncompetitive, low-trapping)
Dextromethadone
REL-1017 / esmethadone (investigational; not yet FDA-approved as of mid-2024)
Dextromethadone (also known as esmethadone or REL-1017) is the dextro-enantiomer of methadone, currently in clinical development as a rapid-onset oral antidepressant. Unlike levo-methadone (the opioid-active enantiomer used in opioid agonist therapy), dextromethadone is a relatively selective NMDA receptor antagonist with low channel-trapping properties and minimal μ-opioid activity. The development hypothesis is that targeting NMDA receptors can produce rapid antidepressant response (like ketamine/esketamine/Auvelity) without the dissociative and abuse-liability profile of ketamine. Phase 3 results have been mixed; FDA approval status uncertain as of mid-2024.
Uncompetitive NMDA receptor antagonist with low channel-trapping (binds open channel briefly, then dissociates, less than ketamine's high-trapping). Weak μ-opioid agonist (~30-fold less than levomethadone). Some 5HT2A and sigma-1 binding.
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
No problems yet. Be the first to suggest one.
+ Add a problemTitration strategies
No titration strategies yet. Be the first to suggest one.
Effects
In trials: generally well-tolerated. Headache, dizziness, nausea reported. Less dissociation than ketamine.
Pharmacodynamics
Interactions
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
How much experience do you have with this combination (1 a little, 5 a lot)?
How did it go? (-100 worst, +100 best)
- checking this mechanism here
Relevant anecdote
No anecdotes yet. Share a relevant one.
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
Pharmacy
Starting dose
Trials use 25 mg or 50 mg PO daily
Preparations
Investigational oral capsule
US FDA Max
Not yet approved
Common uses
Classification(s)
Classes
NMDA receptor antagonist (uncompetitive, low-trapping)
Pharmacology
Routes
Oral
Onset
Rapid (within 1 week in trials)
Duration
Daily dosing
Half-life
Not formally established
Bioavailability
Oral bioavailability suitable for daily dosing
Pregnancy
Investigational
Legal status
Investigational
Purported mechanism
The dextro enantiomer of methadone. Unlike the levo enantiomer (l-methadone), which is a potent μ-opioid agonist, the dextro enantiomer is a relatively selective NMDA receptor antagonist with much weaker μ-opioid activity. Investigated as a rapid-onset antidepressant. Low channel-trapping at NMDA receptor may give it a favorable side-effect profile compared with ketamine (less dissociation, less abuse liability).