Perphenazine blocks dopamine D₂ receptors predominantly, but also may possess antagonist actions against histamine H₁, cholinergic M1 and α₁-adrenergic receptors in the vomiting center leading to reduced nausea and vomiting. Perphenazine binds to dopamine D₂, α_1A-, α_2A-, α_2B-, and α_2C-adrenergic, M3 muscarinic, and histamine H₁ receptors, with Ki values being 1.4, 10, 810.5, 104.9, 85.2, 1848 and 8 nM, respectively. Formulations containing perphenazine have been used for the treatment of schizophrenia and psychosis. The potency of its antiemetic effects is intermediate.

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