5-HT1A partial agonist
5-HT1A serotonin receptor partial agonist
- Anxiolysis
- Presynaptic activity dampens serotonin firing
- Postsynaptic activity → antidepressant effect
- May offset EPS and SRI-induced sexual dysfunction
- Near-full at the autoreceptor, a brake where serotonin is already high
- Offsets EPS caused by antipsychotics by releasing DA in side-effect pathways (similar downstream effect as blocking 5-HT2A)
- May counter SRI-induced sexual dysfunction
- Possibly neuroprotective
- Seemingly all good things
Drugs with this mechanism (18)
- 1-PP — Buspirone metabolite; alpha-2 antagonism that adds noradrenergic activation the parent does not have.
- Aripiprazole — D2 partial agonist; weight-favorable, activating, low prolactin; can cause akathisia.
- Aripiprazole lauroxil LAI — Long-acting aripiprazole prodrug injection for schizophrenia; requires a loading strategy.
- Aripiprazole lauroxil LAI — Rapid-start aripiprazole lauroxil injection used only to initiate Aristada treatment.
- Aripiprazole monohydrate LAI — Extended-interval aripiprazole LAI for schizophrenia and bipolar maintenance.
- Aripiprazole monohydrate LAI — Long-acting aripiprazole for schizophrenia and bipolar maintenance; akathisia remains prominent.
- Brexpiprazole — D2 partial agonist similar to aripiprazole but less activating.
- Buspirone — Non-sedating 5-HT1A partial agonist anxiolytic; no dependence, slow onset.
- Cannabidiol — Purified, nonintoxicating cannabinoid for severe developmental epilepsies.
- Cariprazine — D3-preferring dopamine partial agonist for schizophrenia, bipolar disorder, and adjunctive depression.
- Dehydroaripiprazole — Aripiprazole's long-lived active metabolite, with the same D2 partial agonism and a large share of steady-state exposure.
- Desmethylcariprazine — Cariprazine metabolite with the same D3-preferring partial agonism as the parent.
- Didesmethylcariprazine — Cariprazine's long-lived second metabolite — the reason steady state takes weeks and washout takes longer.
- Lurasidone — Weight-favorable atypical; must be taken with a 350-kcal meal.
- mCPP — Trazodone and nefazodone metabolite; a 5-HT2C agonist that causes anxiety and dysphoria, and accumulates when CYP2D6 is inhibited.
- Norquetiapine — Quetiapine's active metabolite, and the source of the norepinephrine reuptake block and muscarinic blockade the parent lacks.
- Ulotaront — Investigational TAAR1/5-HT1A agonist for schizophrenia without D2 blockade; phase 3 efficacy findings have been disappointing.
- Vilazodone — SSRI plus 5-HT1A partial agonist; take with food for absorption.
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