Sulpiride

Absorption

Sulpiride has an oral bioavailability of 27 ± 9%. A 100-108 mg dose of sulpiride reaches a Cmax of 232-403 ng/mL, with a Tmax of 8.3 h. In another study, the AUC of a 100mg oral dose of sulpiride is 1156 ± 522 h*ng/mL and for an intravenous dose is 3981 ± 813 h*ng/mL.

Toxicity

Patients experiencing an overdose of sulpiride may present with hypotension, sinus tachycardia, arrhythmia, dystonia, CNS depression, hallucinations, vomiting, agitation, dysarthria, salivation, as well as increased muscle tone, hyperreflexia, and extensor plantar reflex. Patients should be treated with symptomatic and supportive treatment.

Chemical properties

Sulpiride is White Solid

Originator

Dogmatil,Delagrange,France,1969

The Uses of Sulpiride

Sulpiride is an antipsychotic drug used in the treatment of Schozophrenia and depression.

The Uses of Sulpiride

dopamine receptor antagonist, antipsychotic

The Uses of Sulpiride

Sulpiride possesses moderate neuroleptic activity along with some stimulating and antidepressant effects. It has antiemetic, moderately cataleptogenic, and antiserotonin action. It facilitates increased blood flow in the stomach. It speeds up the restorative processes in tissues. It is used for schizophrenia, depression, migraines, disturbance of behavioral functions, and stomach and duodenal ulcers.

What are the applications of Application

(RS)-(±)-Sulpiride is a D2DR inhibitor

Indications

Sulpiride is indicated for the treatment of acute and chronic schizophrenia.

Background

Sulpiride first appeared in published literature in 1967. Clinical studies show a greater effect on treating the negative symptoms of schizophrenia rather than positive symptoms at low doses, though the effects are more equal at higher doses.
Sulpiride is not approved by the FDA, Health Canada, or the EMA; though it is approved in individual European countries.

Definition

Sulpiride is a member of the class of benzamides obtained from formal condensation between the carboxy group of 2-methoxy-5-sulfamoylbenzoic acid and the primary amino group of (1-ethylpyrrolidin-2-yl)methylamine.

Manufacturing Process

1-Ethyl-2-aminomethylpyrrolidine is reacted with 2-methoxy-5- sulfamoylbenzoic acid to give sulpiride.

brand name

Dogmatyl (Laboratoires Delagrange, France).

Therapeutic Function

Tranquilizer, Digestive aid

Biological Activity

Standard D 2 -like dopamine receptor antagonist.

Biochem/physiol Actions

(±)-Sulpiride is a D2 dopamine antagonist and an effective treatment for schizophrenia when used in combination with clozapine, a relatively weak D2-dopaminergic antagonist. It is an antipsychotic agent and also exhibits neuroleptic properties but poorly penetrates the central nervous system.45,46

Pharmacokinetics

Sulpiride is a substituted benzamide derivative and a selective dopamine D2 antagonist indicated to treat acute and chronic schizophrenia. It has a short duration of action as it is given twice daily, and a wide therapeutic window as patients have survived single doses as high as 16g. Patients should be counselled regarding increased motor agitation, extrapyramidal reactions, and neuroleptic malignant syndrome.

Clinical Use

Antipsychotic:
Acute and chronic schizophrenia

Synthesis

Sulpiride, N-[(1-ethyl-2-pirrolidinylmethyl]-5-sulfamoyl-O-anizamide (6.7.2), is synthesized from 5-aminosulfosalycilic acid. Methylating this with dimethylsulfate gives 2-methoxy-5-aminosulfonylbenzoic acid (6.7.1), which is transformed into an amide using 2-aminomethyl-1-ethylpyrrolidine as amine components and carbonyl-1,1??-bisimidazole as a condensing agent [70¨C74].

Drug interactions

Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedativeeffects with opioids; increased risk of ventricular arrhythmias with methadone.
Anti-arrhythmics increased risk of ventricular arrhythmias with anti-arrhythmics that prolong the QT interval, e.g. procainamide, disopyramide and amiodarone - avoid with amiodarone.
Antibacterials: increased risk of ventricular arrhythmias with moxifloxacin and parenteral erythromycin - avoid with moxifloxacin.
Antidepressants: possibly increased risk of ventricular arrhythmias and antimuscarinic side effects with tricyclics - avoid.
Antiepileptics: antagonism (convulsive threshold lowered).
Antimalarials: avoid with artemether/lumefantrine.
Antipsychotics: increased risk of ventricular arrhythmias with droperidol, haloperidol and pimozide - avoid; possible increased risk of ventricular arrhythmias with risperidone.
Antivirals: concentration possibly increased by ritonavir.
Anxiolytics and hypnotics: increased sedative effects.
Atomoxetine: increased risk of ventricular arrhythmias.
Beta-blockers: enhanced hypotensive effect; increased risk of ventricular arrhythmias with sotalol.
Cytotoxics: increased risk of ventricular arrhythmias with vandetanib - avoid; increased risk of ventricular arrhythmias with arsenic trioxide.
Diuretics: enhanced hypotensive effect.
Lithium: increased risk of extrapyramidal side effects and possibly neurotoxicity.
Pentamidine: increased risk of ventricular arrhythmias.

Metabolism

95% of a dose of sulpiride is not metabolized.

Metabolism

Sulpiride undergoes little metabolism.
95% of a dose is excreted in the urine and faeces, mainly as unchanged drug.

storage

Room temperature