Sulpiride: an antipsychotic with selective dopaminergic antagonist properties.

To review the pharmacology, pharmacokinetics, clinical investigations, and adverse effects of sulpiride as a treatment for schizophrenia. Information was selected from a MEDLINE search of English-language medical literature using "sulpiride" as the search term. Manual searches of pertinent journal article bibliographies also were performed. Clinical investigations with a blind, controlled, randomized design and treatment durations of at least 6 weeks were preferred. Formal assessment of a patient's schizophrenia was required. One clinical investigation using a 4-week treatment duration and 1 open investigation were included for purposes of adverse reaction assessment. Clinical investigations were evaluated for design, sample size, diagnosis, duration, and outcome. Data from all investigations were selected by 1 author and reviewed by both authors. Sulpiride is a substituted benzamide with selective dopaminergic blocking activity. Early pharmacology reports hypothesized that sulpiride was selective for dopamine (D)2 receptors only, but sulpiride also blocks D3 and D4 receptors. Sulpiride does not block D1, adrenergic, cholinergic, gamma-aminobutyric acid-ergic, histaminergic, or serotonergic receptors to an appreciable extent. The oral bioavailability of sulpiride is poor, with estimates approximating 35%. Sulpiride does not appear to have an extensive first-pass metabolism, nor is it extensively protein-bound. There have been no identified active metabolites, and elimination appears to depend primarily on the kidneys. Clinical studies support sulpiride as being equally effective as active controls in the acute treatment of patients with schizophrenia. Daily doses permitted in these clinical investigations ranged from 100 to 3200 mg. Further investigation is required to determine the usefulness of sulpiride as a chronic treatment of schizophrenia and its effectiveness in treating the negative symptoms of schizophrenia. Sulpiride may cause extrapyramidal effects, autonomic effects, tardive dyskinesia, and the neuroleptic malignant syndrome. The incidence of these adverse reactions has not been established. Sulpiride is a safe and effective pharmacotherapeutic treatment for the acute management of schizophrenia. A unique pharmacology does not appear to provide sulpiride with a greater effectiveness than the standard antipsychotics, but may provide it with minor safety advantages.