Sigma-1 antagonist
Sigma-1 receptor antagonist
- Blocks sigma-1 chaperone signaling
- Not a neurotoxic mechanism, but could theoretically interfere with neuroprotective mechanisms σ1 agonists
- Could interfere with the σ1-based antidepressant effect of Auvelity
Drugs with this mechanism (8)
- Fluphenazine — High-potency phenothiazine, available as a long-acting depot.
- Fluphenazine decanoate LAI — High-potency first-generation antipsychotic depot; inexpensive but extrapyramidal-effect heavy.
- Fluphenazine injection — Short-acting IM high-potency antipsychotic for acute psychosis; about a third to half the oral dose, then back to tablets.
- Haloperidol — Prototypical high-potency typical antipsychotic; potent D2 blocker, high EPS risk.
- Haloperidol decanoate LAI — First-generation D2-antagonist depot for schizophrenia maintenance; EPS burden is high.
- Haloperidol injection — Parenteral high-potency D2 antipsychotic for acute agitation; IV use magnifies QT concern.
- Perphenazine — Mid-potency typical; performed comparably to atypicals in CATIE.
- Sertraline — Broadly indicated SSRI with few CYP interactions; prominent early GI effects.
Self-check
- Is sigma-1 antagonism described as directly neurotoxic?
No; interference with neuroprotection is theoretical. - Which drug’s sigma-1-based antidepressant effect could be interfered with?
Auvelity’s.
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