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Amisulpride is a second-generation (atypical) antipsychotic and a substituted benzamide derivative. It acts as a selective antagonist at dopamine D2 and D3 receptors, with a unique dose-dependent pharmacological profile. At low doses, it preferentially blocks presynaptic D2/D3 receptors, thereby increasing dopaminergic transmission, which is thought to alleviate negative symptoms of schizophrenia and depressive symptoms in dysthymia. At higher doses, it blocks postsynaptic D2/D3 receptors, effectively treating the positive symptoms of schizophrenia. Unlike many other antipsychotics, amisulpride has low affinity for D1, D4, and D5 receptors, as well as alpha-adrenergic, histamine, and cholinergic receptors, leading to a distinct side-effect profile. It also acts as a potent antagonist at the 5-HT7 and 5-HT2B receptors. Originally developed by Sanofi for psychiatric indications, an intravenous formulation was later developed by Acacia Pharma and approved for the prevention and treatment of postoperative nausea and vomiting (PONV).
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