Sigma-1 agonist
Sigma-1 receptor agonist
- Sigma-1 is an ER-membrane chaperone
- Regulates calcium signaling and protein trafficking
- May facilitate NMDA surface expression
Sigma-1 agonist (1/3)
- ➔ facilitates NMDA receptor surface expression
- ➔ neuroprotective effects (preclinical evidence)
- ➔ potential relevance to mood disorders with glutamatergic dysregulation
- ➔ putative anti-inflammatory and antiviral effects σ1 agonists ranked by ~binding affinity
Sigma-1 agonist (2/3)
- ➔ considered a principal mechanism of Auvelity (depression) and Nuedexta (pseudobulbar affect)
- ➔ likely contributes to antiseizure mechanism
Sigma-1 agonist (3/3)
- Putative endogenous σ1 agonists: DMT, DHEA, pregnenolone
Drugs with this mechanism (9)
- Dextromethorphan — OTC cough suppressant; NMDA antagonist and sigma-1 agonist, dissociative in overdose.
- Dextrorphan — Dextromethorphan's active metabolite; the NMDA antagonism behind both the dissociative effect and the abuse potential.
- Dehydroepiandrosterone — Adrenal precursor of testosterone and estradiol, and a sigma-1 agonist in the central nervous system.
- DHEAS — The sulfated, circulating reservoir form of DHEA; a negative modulator at GABA-A.
- N,N-dimethyltryptamine — Short-acting serotonergic psychedelic; the active principle of ayahuasca.
- Fenfluramine — Serotonin releaser once in "fen-phen"; now for Dravet seizures, valvulopathy risk.
- Fluvoxamine — Sigma-1-active SSRI and strong CYP1A2 inhibitor; more GI upset than other SSRIs.
- Fluvoxamine CR — Controlled-release fluvoxamine for OCD and social anxiety; a potent CYP1A2 inhibitor.
- Pregnenolone — The steroid every other steroid hormone is built from; a sigma-1 agonist, sold over the counter.
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