Dextromethadone - Revision history

CategoryClaude: Sentence-case category link per house style (NMDA_Receptor_Antagonists → NMDA_receptor_antagonists)

2026-05-23T05:02:23Z

Sentence-case category link per house style (NMDA_Receptor_Antagonists → NMDA_receptor_antagonists)

← Older revision		Revision as of 05:02, 23 May 2026
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	[[Category:NMDA ~~Receptor Antagonists~~]]		[[Category:NMDA receptor antagonists]]
	[[Category:Antidepressants]]		[[Category:Antidepressants]]
	[[Category:Dissociatives]]		[[Category:Dissociatives]]

MDElliottMD: Em-dash sweep: replace em-dash with comma per project rule; PendellsCorner verbatim quotes preserved.

2026-05-19T03:16:07Z

Em-dash sweep: replace em-dash with comma per project rule; PendellsCorner verbatim quotes preserved.

← Older revision		Revision as of 03:16, 19 May 2026
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	\| 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 — less than ketamine's high-trapping). Weak μ-opioid agonist (~30-fold less than levomethadone). Some 5HT2A and sigma-1 binding.		\| 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/>

Maintenance script: Create Dextromethadone page (Stahl-sourced detail with skepticism)

2026-05-16T01:56:00Z

Create Dextromethadone page (Stahl-sourced detail with skepticism)

New page

{{MedTemplate
| brand = REL-1017 / esmethadone (investigational; not yet FDA-approved as of mid-2024)
| classes = NMDA receptor antagonist (uncompetitive, low-trapping)
| 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).
| uses = Investigational for major depressive disorder; trials underway (phase 3 mixed results)
| starting_dose = Trials use 25 mg or 50 mg PO daily
| preparations = Investigational oral capsule
| fda_max = Not yet approved
| routes = Oral
| onset = Rapid (within 1 week in trials)
| duration = Daily dosing
| halflife = Not formally established
| bioavailability = Oral bioavailability suitable for daily dosing
| pregnancy = 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.
| 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.
| interactions = <pharmaInteractions/>
}}

[[Category:NMDA Receptor Antagonists]]
[[Category:Antidepressants]]
[[Category:Dissociatives]]