Sulpiride's primary use in medicine is in the management of the symptoms of schizophrenia. It has been used as both a monotherapy and adjunctive therapy in schizophrenia. It has also been used in the treatment of dysthymia. There is evidence, although low quality that with sulpiride could accelerate antidepressant response in patients with major depressive disorder. There is also evidence of its efficacy in treating panic disorder. Sulpiride is indicated for the treatment of vertigo in some countries. In Japan, Sulpiride is both approved as a treatment for schizophrenia and for major depressive disorder.
Contraindications
Contraindications
Hypersensitivity to sulpiride
Pre-existing breast cancer or other prolactin-dependent tumors
Lithium use — increased risk of neurological side effects of both drugs
Pregnancy and lactation
Pregnancy: Animal studies did not reveal any embryotoxicity or fetotoxicity, nor did limited human experience. Due to insufficient human data, pregnant women should be treated with sulpiride only if strictly indicated. Additionally, the newborns of treated women should be monitored, because isolated cases of extrapyramidal side effects have been reported.
Lactation: Sulpiride is found in the milk of lactating women. Since the consequences are unclear, women should not breastfeed during treatment.
Side effects
Sulpiride is usually well tolerated, producing few adverse effects. Their incidences are as follows: ; Common adverse effects:
Tardive dyskinesia — a rare, often permanent movement disorder that, more often than not, results from prolonged treatment with antidopaminergic agents such as antipsychotics. It presents with slow, involuntary, repetitive and purposeless movements that most often affect the facial muscles.
Neuroleptic malignant syndrome — a rare, life-threatening complication that results from the use of antidopaminergic agents. Its incidence increases with concomitant use of lithium salts
Blood dyscrasias — rare, sometimes life-threatening complications of the use of a number of different antipsychotics which involves abnormalities in the composition of a person's blood. Examples include:
Sulpiride has a relatively low order of acute toxicity. Substantial amounts may cause severe but reversible dystonic crises with torticollis, protrusion of the tongue, and/or trismus. In some cases all the classical symptoms typical of severe Parkinson's disease may be noted; in others, over-sedation/coma may occur. The treatment is largely symptomatic. Some or all extrapyramidal reactions may respond to the application of anticholinergic drugs such as biperiden or benzatropine. All patients should be closely monitored for signs of long QT syndrome and severe arrhythmias.
Interactions
Sulpiride neigher inhibits nor stimulates cytochrome P450 family of oxidizing enzymes in human, thus would not cause clinically significant interactions with other drugs, which are metabolized by CYPs. However, the risk or severity of adverse effects can be increased when sulpiride is combined with other drugs, but this is not related to substrates, inducers and inhibitors of CYPs.
Pharmacology
Pharmacodynamics
Sulpiride is a selectiveantagonist at dopamine D2, D3 and 5-HT1A receptors. Antagonism at 5-HT1A dominates in doses exceeding 600 mg daily. In doses of 600 to 1,600 mg sulpiride shows mild sedating and antipsychotic activity. Its antipsychotic potency compared to chlorpromazine is only 0.2. In low doses its prominent feature is antagonism of presynaptic inhibitory dopamine and serotonin receptors, accounting for some antidepressant activity and a stimulating effect. Additionally, it alleviates vertigo. The benzamide neuroleptics have been shown to activate the endogenous gamma-hydroxybutyrate receptor in vivo at therapeutic concentrations. Sulpiride was found in one study in rats to upregulate GHB receptors. GHB has neuroleptic properties and it is believed binding to this receptor may contribute to the effects of these neuroleptics. Sulpiride, along with clozapine, has been found to activate DNA demethylation in the brain.
Chemistry
Synthesis
Sulpiride can be synthesized from 5-aminosulfosalicylic acid. Methylating this with dimethylsulfate gives 2-methoxy-5-aminosulfonylbenzoic acid, which is transformed into an amide using 2-aminomethyl-1-ethylpyrrolidine as the amine component and carbonyldiimidazole as a condensing agent.
History
Sulpiride was discovered as a result of a research program by Justin-Besançon and C. Laville at Laboratoires Delagrange who were working to improve the anti-dysrhythmic properties of procainamide; the program led first to metoclopramide and later to sulpiride. Laboratoires Delagrange was acquired by Synthelabo in 1991 which eventually became part of Sanofi.
Society and culture
Brand names
Sulpiride is marketed under the brand names Dogmatil, Dolmatil, Eglonyl, Espiride, Modal, Prometar, and Sulpor, among many others.
Medicinal forms
These include tablet and oral solution
Research
Sulpiride has been studied for use as a hormonal contraceptive in women in whom conventional oral contraceptives are contraindicated and to potentiate progestogen-only contraceptives. The contraceptive effects of sulpiride are due to its prolactin-releasing and antigonadotropic effects and the hyperprolactinemia–amenorrhea state that it induces.
