5-HT2A agonist
5-HT2A serotonin receptor agonist
- If BBB-crossing: ↑ cortical glutamate signaling → psychedelic effects
- Key receptor driving serotonin toxicity
- Tolerance to psychedelic effects develops within days via receptor downregulation
5-HT2A agonist (1/2)
- ↑ glutamate release in cortex
- ↓ DA release in nigrostriatal pathway
- ➔ SSRI-induced akathisia
- Implicated in SSRI sexual dysfunction (also 5-HT2C)
- Associated with rapid antidepressant effect (clinical trials)
- Serotonin toxicity is driven primarily by 5-HT2A overstimulation
- Altered emotional processing
- Promotes synaptic plasticity (preclinical data)
5-HT2A agonist (2/2)
- Pupillary dilation
- Increased heart rate
Drugs with this mechanism (8)
- N,N-dimethyltryptamine — Short-acting serotonergic psychedelic; the active principle of ayahuasca.
- Ergotamine — Ergot alkaloid for migraine; vasoconstrictive, largely supplanted by triptans.
- Lysergic acid diethylamide — Classic serotonergic psychedelic; potent 5-HT2A agonist.
- mCPP — Trazodone and nefazodone metabolite; a 5-HT2C agonist that causes anxiety and dysphoria, and accumulates when CYP2D6 is inhibited.
- Methylenedioxymethamphetamine — Serotonin releaser (empathogen) under study for PTSD.
- Mescaline — Classic peyote psychedelic; a 5-HT2A agonist.
- Psilocin — The active dephosphorylated form of psilocybin; a 5-HT2A agonist.
- Serotonin — The endogenous ligand at fourteen receptor subtypes; the home of serotonicity — synaptic serotonin elevation.
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