D2 partial agonist
D2 dopamine receptor partial agonist
- Stabilizes D2 signaling: antagonistic where dopamine is high, agonistic where it is low
- Antipsychotic effect with less prolactin elevation/EPS than full blockade
- Akathisia is common
- Antipsychotic effect of “A, B, & C,” listed with approximate intrinsic efficacy at D2 (relative to dopamine = 100%; haloperidol ~0%)
- Lower risk of acute dystonia and tardive dyskinesia than full D2 antagonists
- ➔ not zero risk; TD cases reported
- May decrease prolactin
Drugs with this mechanism (12)
- 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.
- 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.
- Lysergic acid diethylamide — Classic serotonergic psychedelic; potent 5-HT2A agonist.
- Norclozapine — Active clozapine metabolite; M1 agonist implicated in some clozapine effects.
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