Sulpiride

Sulpiride

Clinical data
Trade names	Dogmatil, Others
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth (tablets, capsules, solution), intramuscular injection
ATC code	N05AL01 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)[1] UK: POM (Prescription only) In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	25–40%[2][3]
Protein binding	<40%[2]
Metabolism	Not metabolized;[5][6][7][8][9] 95% is exerted as the unchanged drug[2][5]
Elimination half-life	6–8 hours[2][4]
Excretion	Urine (70–90%),[4][3] Feces.[5]
Identifiers
IUPAC name N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide
JSmol)	Interactive image
SMILES NS(=O)(=O)c1ccc(OC)c(c1)C(=O)NCC1CCCN1CC
InChI InChI=1S/C15H23N3O4S/c1-3-18-8-4-5-11(18)10-17-15(19)13-9-12(23(16,20)21)6-7-14(13)22-2/h6-7,9,11H,3-5,8,10H2,1-2H3,(H,17,19)(H2,16,20,21) Y Key:BGRJTUBHPOOWDU-UHFFFAOYSA-N Y
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Sulpiride, sold under the brand name Dogmatil among others, is an

Sulpiride's primary use in medicine is in the management of the symptoms of schizophrenia.^[2] It has been used as both a monotherapy and adjunctive therapy (in case of treatment-resistance) in schizophrenia.^{[2][11][12][13][14][15]} It has also been used in the treatment of dysthymia.^[16] There is evidence, although low quality, that Sulpiride could accelerate antidepressant response in patients with major depressive disorder.^[17] There is also evidence of its efficacy in treating panic disorder.^[18][19] Sulpiride is indicated for the treatment of vertigo in some countries.^[20] In Japan, Sulpiride is both approved as a treatment for schizophrenia and for major depressive disorder (low dose).^[21][22]

Contraindications

Contraindications^[2]

• 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^[2]

• Pre-existing Parkinson's disease
• Patients under 18 years of age (insufficient clinical data)
• Pre-existing severe heart disease/
  arrhythmias
  )
• Patients with pre-existing epilepsy. Anticonvulsant therapy should be maintained
• 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.^[2]
• Lactation: Sulpiride is found in the milk of lactating women. Since the consequences are unclear, women should not breastfeed during treatment.^[2]

Side effects

Sulpiride is usually well tolerated, producing few adverse effects. Their incidences are as follows:^{[2][11][23][24][25][26][27][28][29]}

Common (>1%) adverse effects

• Dizziness
• Headache
• Extrapyramidal side effects

- Tremor

- Dystonia

- Akathisia — a sense of inner restlessness that presents itself with the inability to stay still

- Parkinsonism

• Somnolence (not a very prominent adverse effect considering its lack of α₁ adrenergic, histamine and muscarinic acetylcholine receptor affinity)
• Insomnia
• Weight gain or loss
• Hyperprolactinemia (elevated plasma levels of the hormone, prolactin which can, in turn lead to sexual dysfunction, galactorrhea, amenorrhea, gynecomastia
  , etc.)
• Nausea
• Vomiting
• Nasal congestion
• Anticholinergic adverse effects such as:

- Dry mouth

- Constipation

- Blurred vision

• Impaired concentration

Rare (<1% incidence) adverse effects

• Tardive dyskinesia — a rare, often permanent^{[citation needed]} 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:

- Agranulocytosis — a significant drop in white blood cell count, leaving individuals wide open to life-threatening opportunistic infections

- Neutropenia

-

Leucopenia

- Leukocytosis^[30]

• Seizures
• Torsades de pointes

Unknown incidence adverse effects include

• arrhythmias
  .
• Cholestatic jaundice^[31]
• Elevated liver enzymes
• Primary biliary cirrhosis^[32]
• 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)

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 benzatropine. All patients should be closely monitored for signs of long QT syndrome and severe arrhythmias.

Interactions

Sulpiride neither inhibits nor stimulates

Sulpiride, along with clozapine, and valproate has been found to activate DNA demethylation in the brain.^[36]

History

Sulpiride was discovered in 1966 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.^[37][38] Laboratoires Delagrange was acquired by Synthelabo in 1991^[39][40] which eventually became part of Sanofi.^[41]

Society and culture

Brand names

Sulpiride is marketed under the brand names Dogmatil (

These include tablet and oral solution[43]

Patient Aversions

Some individuals from the Caribbean region may have an aversion to taking the medication due to the association with the brand name of Dogmatil. Dogmatil has been associated with dog medication.

Research

Sulpiride has been studied for use as a

Since the use of psychotropic drugs is efficient in treating irritable bowel syndrome (IBS),^[46] sulpiride is studied as potential sole maintenance therapy in the treatment of IBS.^[47][48][46]

References