Dextromethadone: Difference between revisions
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| 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/> | ||