D1 antagonist
D1 dopamine receptor antagonist
- Little EPS (extrapyramidal symptoms) compared with D2 blockade
- Theoretical contribution to motor slowing if combined with D2 blockade
- May worsen cognition/negative symptoms by reducing cortical D1 tone
- D1 blockade occurs incidentally with some antipsychotics but is not a therapeutic target
- Could theoretically attenuate stimulant benefit for ADHD
Drugs with this mechanism (12)
- Loxapine inhaled — Inhaled loxapine for acute agitation; single-use inhaler under a bronchospasm REMS.
- Asenapine — Sublingual/transdermal atypical; oral tablets are ineffective if swallowed.
- Asenapine transdermal — Once-daily asenapine patch - the only transdermal antipsychotic.
- 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.
- Loxapine — Mid-potency typical; an inhaled form treats agitation.
- Norclozapine — Active clozapine metabolite; M1 agonist implicated in some clozapine effects.
- Olanzapine — Highly effective atypical; among the worst for weight gain and metabolic effects.
- Olanzapine IM — Rapid intramuscular olanzapine for acute agitation; sedating and anticholinergic.
- Olanzapine pamoate LAI — Olanzapine LAI; post-injection delirium/sedation risk mandates 3-hour observed dosing.
- Olanzapine SubQ LAI — Monthly subcutaneous olanzapine depot; no post-injection syndrome in the boxed warning; 46.5-day half-life.
Self-check
- How does D1 blockade’s EPS burden compare with D2 blockade?
Much lower. - How may cortical D1 blockade affect cognition?
It may worsen cognition.
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