Sulpiride

Last updated

Sulpiride
Sulpiride.svg
Sulpiride ball-and-stick.png
Clinical data
Trade names Dogmatil, Others
AHFS/Drugs.com International Drug Names
Routes of
administration 		By mouth (tablets, capsules, solution), intramuscular injection
ATC code
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; [4] [5] [6] [7] [8] 95% is exerted as the unchanged drug [2] [4]
Elimination half-life 6–8 hours [2] [9]
Excretion Urine (70–90%), [9] [3]
Feces. [4]
Identifiers
  • N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.036.124 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H23N3O4S
Molar mass 341.43 g·mol−1
3D model (JSmol)
  • NS(=O)(=O)c1ccc(OC)c(c1)C(=O)NCC1CCCN1CC
  • 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) Yes check.svgY
  • Key:BGRJTUBHPOOWDU-UHFFFAOYSA-N Yes check.svgY
   (verify)

Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic (although some texts have referred to it as a typical antipsychotic) [10] medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and is sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Asia, Central America, Europe, South Africa and South America. Levosulpiride is its purified levo-isomer and is sold in India for similar purposes. It is not approved in the United States, Canada, or Australia. The drug is chemically and clinically similar to amisulpride.

Contents

Medical uses

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]

Cautions [2]

Pregnancy and lactation

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
- Tremor
- Dystonia
- Akathisia — a sense of inner restlessness that presents itself with the inability to stay still
- Parkinsonism
- Dry mouth
- Constipation
- Blurred vision
Rare (<1% incidence) adverse effects
- Agranulocytosis — a significant drop in white blood cell count, leaving individuals wide open to life-threatening opportunistic infections
- Neutropenia
- Leucopenia
- Leukocytosis [30]
Unknown incidence adverse effects include

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 cytochrome P450 family (CYP) of oxidizing enzymes in human, thus would not cause clinically significant interactions with other drugs, [5] 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 [33]
Receptor Affinity (Ki, nM)
DAT >10,000
5-HT1A >10,000
5-HT2A 4,786
5-HT3 >10,000
5-HT6 5,011[ unreliable source? ]
5-HT7 5,011[ unreliable source? ]
α1 >10,000
α2 >10,000
D1 >10,000
D2 9.8
D3 8.05
D4 54
H1 >10,000
V3 >10,000
Affinity values are toward cloned human receptors.

Sulpiride is a selective antagonist at dopamine D2, D3 and to a lesser extent D4 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 (1/5). In low doses (in particular 50 to 200 mg daily) 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 (including sulpiride, amisulpride, and sultopride) have been shown to activate the endogenous gamma-hydroxybutyrate receptor in vivo at therapeutic concentrations. [34] Sulpiride was found in one study in rats to upregulate GHB receptors. [35] GHB has neuroleptic properties and it is believed binding to this receptor may contribute to the effects of these neuroleptics.

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 (DE, HK, SG, PH), Dolmatil (IE, UK, NL), Eglonyl (RU, ZA, HR, SI), Espiride (ZA), Modal (IL), Prometar (UY), Equilid (BR) and Sulpor (UK), among many others. [42]

Medicinal forms

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 hormonal contraceptive in women in whom conventional oral contraceptives are contraindicated and to potentiate progestogen-only contraceptives. [44] [45] The contraceptive effects of sulpiride are due to its prolactin-releasing and antigonadotropic effects and the hyperprolactinemia–amenorrhea state that it induces. [44] [45]

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]

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Clozapine</span> Atypical antipsychotic medication

Clozapine is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. It is also used for the treatment of psychosis in Parkinson's disease.

<span class="mw-page-title-main">Neuroleptic malignant syndrome</span> Medical condition

Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotic (neuroleptic) medications. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures.

<span class="mw-page-title-main">Chlorpromazine</span> Antipsychotic medication

Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Typical antipsychotic</span> Class of drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders with typical antipsychotics.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Risperidone</span> Antipsychotic medication

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

<span class="mw-page-title-main">Progabide</span> Pharmaceutical drug

Progabide is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist of the GABAA, GABAB, and GABAA-ρ receptors.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Flupentixol</span> Typical antipsychotic drug of the thioxanthene class

Flupentixol (INN), also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol . Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Melperone</span> Antipsychotic drug

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<span class="mw-page-title-main">Tiapride</span> Antipsychotic medication

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<span class="mw-page-title-main">Perospirone</span> Atypical antipsychotic medication

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<span class="mw-page-title-main">Levosulpiride</span> Antipsychotic and prokinetic medication

Levosulpiride, sold under the brand name SULPEPTA , is a potent prokinetic agent of the benzamide class. It is a selective antagonist of the dopamine D2 receptors and 5-HT4 agonist on both central and peripheral nervous systems. Levosulpiride is claimed to have mood elevating properties.

<span class="mw-page-title-main">Clocapramine</span> Antipsychotic medication

Clocapramine, also known as 3-chlorocarpipramine, is an atypical antipsychotic of the iminostilbene class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia. In addition to psychosis, clocapramine has also been used to augment antidepressants in the treatment of anxiety and panic.

References

  1. ↑ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. 1 2 3 4 5 6 7 8 9 10 11 "Sulpiride Tablets 200mg, 400mg (SPC)". electronic Medicines Compendium (eMC). Sanofi. 21 January 2010. Archived from the original on 19 October 2013. Retrieved 19 October 2013.
  3. 1 2 Bressolle F, Brès J, Fauré-Jeantis A (January 1992). "Absolute bioavailability, rate of absorption, and dose proportionality of sulpiride in humans". Journal of Pharmaceutical Sciences. 81 (1): 26–32. doi:10.1002/jps.2600810106. PMID   1619566.
  4. 1 2 3 Imondi AR, Alam AS, Brennan JJ, Hagerman LM (March 1978). "Metabolism of sulpiride in man and rhesus monkeys". Archives Internationales de Pharmacodynamie et de Therapie. 232 (1): 79–91. PMID   96745.
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  36. ↑ Dong E, Nelson M, Grayson DR, Costa E, Guidotti A (September 2008). "Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation". Proceedings of the National Academy of Sciences of the United States of America. 105 (36): 13614–9. Bibcode:2008PNAS..10513614D. doi: 10.1073/pnas.0805493105 . PMC   2533238 . PMID   18757738.
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  41. ↑ Meek T (24 May 2013). "A look back at Sanofi's merger with Synthélabo". PMLiVE.
  42. ↑ "Sulpiride". Drugs.com.
  43. ↑ "Sulpiride 200mg/5ml Oral Solution". EMC. Datapharm.
  44. 1 2 Buvat J, Decroix-Blacker C, Legal F, Gasnault JP (January 1976). "[One thousand months of contraception with sulpiride]". Revue Française de Gynécologie et d'Obstétrique (in French). 71 (1): 53–61. PMID   959705. Archived from the original on 15 April 2018. Retrieved 15 April 2018.
  45. 1 2 Payne MR, Howie PW, McNeilly AS, Cooper W, Marnie M, Kidd L (August 1985). "Sulpiride and the potentiation of progestogen only contraception". British Medical Journal. 291 (6495): 559–61. doi:10.1136/bmj.291.6495.559. PMC   1418199 . PMID   2994800.
  46. 1 2 Sato M, Murakami M (August 2006). "[Treatment for irritable bowel syndrome--psychotropic drugs, antidepressants and so on]". Nihon Rinsho (in Japanese). 64 (8): 1495–500. PMID   16898620.
  47. ↑ El-Reshaid K, Al-Bader S (2019). "New regimen for treatment of irritable bowel syndrome with emphasis on Sulpride as the sole maintenance therapy". Journal of Drug Delivery and Therapeutics. 9 (5): 154–157. doi: 10.22270/jddt.v9i5.3424 . S2CID   208163204.
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