A Comprehensive Monograph on Sulpiride: Pharmacology, Clinical Utility, and Safety Profile

Executive Summary

Sulpiride is a substituted benzamide derivative with a unique pharmacological profile that positions it distinctly within the class of antipsychotic agents. First described in the 1960s, it functions primarily as a selective antagonist of dopamine D2 and D3 receptors. Its most notable characteristic is a dose-dependent bimodal mechanism of action: at low doses, it exhibits a disinhibitory, antidepressant effect by blocking presynaptic autoreceptors, thereby enhancing dopaminergic neurotransmission; at higher doses, it exerts a conventional postsynaptic blockade, producing antipsychotic effects. This dual action underpins its wide therapeutic applications, which include the treatment of acute and chronic schizophrenia, depressive and anxiety disorders, vertigo, and certain functional gastrointestinal conditions.

Pharmacokinetically, Sulpiride is characterized by poor and variable oral bioavailability, which is further reduced by food intake. It undergoes minimal metabolism and is eliminated almost entirely unchanged via renal excretion, a factor that necessitates careful dose adjustments in patients with renal impairment and in the elderly. Its safety profile is marked by a significant risk of dopamine-mediated adverse effects, including extrapyramidal symptoms (EPS) and hyperprolactinemia, with a frequency and severity that can be comparable to older, "typical" antipsychotics. However, due to its high receptor selectivity, it is associated with a lower incidence of anticholinergic, antihistaminic, and alpha-adrenergic side effects like sedation and orthostatic hypotension.