Sulpiride
Sulpiride (brand names Dogmatil (HK, SG, PH), Dolmatil (IE, UK), Eglonyl (RU, ZA), Espiride (ZA), Modal (IL), Sulpor (UK) and others) is an atypical antipsychotic drug (although some texts have referred to it as a typical antipsychotic) of the benzamide class used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Europe, Russia and Japan. Levosulpiride is its purified levo-isomer and is sold in India for similar purpose. So far it has not been approved in the United States, Canada and Australia. The drug is chemically and clinically similar to amisulpride.

# Medical uses
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 case of treatment-resistance) in schizophrenia. It has also been used in the treatment of dysthymia. Augmentation with sulpiride has also been tried as a strategy for accelerating antidepressant response in patients with major depressive disorder. There is also evidence of its efficacy in treating panic disorder.

## 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.

# Adverse effects
Sulpiride is usually well-tolerated, producing few adverse effects. Their incidences are as follows:
- Dizziness
- Headache
- Extrapyramidal side effects
- Somnolence (not a very prominent adverse effect considering its lack of alpha-1 adrenergic, histamine and muscarinic acetylcholine receptor affinity)
- Insomnia
- Weight gain or loss
- Hyperprolactinaemia (elevated plasma levels of the hormone, prolactin which can, in turn lead to sexual dysfunction, galactorrhoea, amenorrhoea, gynaecomastia, etc.)
- Nausea
- Vomiting
- Nasal congestion
- Anticholinergic adverse effects such as:
- Restlessness
- Impaired concentration
- 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 (hence tardive), 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 (medication) salts.
- Blood dyscrasias  rare, sometimes life-threatening complications of the use of a number of different antipsychotics (most notably clozapine) which involves abnormalities in the composition of a person's blood (e.g. having too few white blood cells per unit volume of blood. Examples include:
- Seizures
- Torsades de Pointes
- QTc interval prolongation which can lead to potentially fatal arrhythmias.
- Cholestatic jaundice
- Elevated liver enzymes
- Primary biliary cirrhosis
- Allergic reactions
- Photosensitivity  sensitivity to light.
- Skin rashes
- Depression
- Catatonia
- Palpitations
- Agitation
- Diaphoresis  sweating without a precipitating factor (e.g. increased ambient temperature).
- Hypotension  low blood pressure.
- Hypertension  high blood pressure.
- Venous thromboembolism (probably rare)

## Contraindications and cautions
Contraindications
- Hypersensitivity to sulpiride
- Pre-existing breast cancer or other prolactin-dependent tumors
- Phaeochromocytoma
- Intoxication with other centrally active drugs
- Concomitant use of levodopa
- Acute porphyria
- Comatose state or CNS depression
- Bone-marrow suppression
Cautions
- Pre-existing Parkinson's Disease
- Patients below 18 years of age (insufficient clinical data)
- Pre-existing severe heart disease/bradycardia, or hypokalemia (predisposing to long QT syndrome and severe arrhythmias)
- Patients with pre-existing epilepsy. Anticonvulsant therapy should be maintained.
- Lithium use  increased risk of neurological side effects of both drugs

## Overdose
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 benztropine. All patients should be closely monitored for signs of long-QT syndrome and severe arrhythmias.

# 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 (CDI) as a condensing agent.

# Pharmacology
Sulpiride is a selective antagonist at dopamine D2 and D3 receptors. This action 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 (1/5). In low doses (in particular 50 to 200 mg daily) its prominent feature is antagonism of presynaptic inhibitory dopamine receptors accounting for some antidepressant activity and a stimulating effect. Therefore, it is in these doses used as a second line antidepressant. Additionally, it alleviates vertigo.
The benzamide neuroleptics (including sulpiride, amisulpride, and sultopride) 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.