Tiapride

Last updated
Tiapride
Tiapride.svg
Clinical data
Trade names Tiapridal
Routes of
administration 		Oral (tablets), IM, IV
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances) [1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ~75% (oral) (Tmax = 1 hour)
Protein binding Negligible
Elimination half-life 2.9–3.6 hours
Excretion Urine (70% as unchanged tiapride)
Identifiers
  • N-[2-(diethylamino)ethyl]-2-methoxy-5-methylsulfonylbenzamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.051.717 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H24N2O4S
Molar mass 328.43 g·mol−1
3D model (JSmol)
  • CCN(CC)CCNC(=O)C1=C(C=CC(=C1)S(=O)(=O)C)OC
   (verify)

Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. [2] A derivative of benzamide, tiapride is chemically and functionally similar to other benzamide antipsychotics such as sulpiride and amisulpride known for their dopamine antagonist effects.

Contents

Medical uses

Alcoholism

Research in animal models and clinical studies in alcoholic patients have found that tiapride has anxiolytic effects. Dopamine hyperactivity has been linked with alcohol withdrawal syndrome (AWS), suggesting that tiapride's antidopaminergic effects are the most likely mechanism for its clinical efficacy, [3] although others believe some other mechanism might be involved. [4] Alcoholic patients treated with tiapride at a dosage of 300 mg/day reported reduced psychological distress and improved abstinence from alcohol. [4] In another study in which alcoholic patients were given titrated doses up to 800 mg/day, subjects showed significant improvements in ratings of withdrawal, craving, psychiatric symptoms and quality of life. [3]

While tiapride does not affect positive symptoms of psychosis such as hallucinosis or delirium sometimes manifested in alcohol withdrawal syndrome, if combined with a drug such as carbamazepine that addresses those symptoms, it is ideal for treating alcohol dependency because its metabolism does not depend on liver function and it has low potential for abuse. [3] This sets it apart from the benzodiazepines, which are contraindicated with alcohol and can be addictive. [4] Moreover, tiapride's rapid onset makes intravenous or intramuscular injection prior to or during withdrawal episodes particularly effective. [3]

Agitation and aggression

Agitation and aggression are also associated with hyperdopaminergic activity. Antipsychotic drugs are the most common treatment for these symptoms, but often come with a host of side-effects including orthostatic hypotension and deficits in vigilance and attention. One clinical study in agitated elderly patients compared the effects of tiapride, haloperidol and placebo and found that while the two drugs had comparable efficacy superior to the placebo effect, tiapride had fewer and less severe side effects than haloperidol. [5]

Tiapride's selectivity for the limbic system, which is associated with emotion, could underlie its particular efficacy in treating these affective disorders. Moreover, its selectivity for the dopaminergic system is thought to account for its avoidance of the side effects typically associated with other neuroleptic drugs, such as chlorpromazine, which act on a number of neurotransmitter systems. [2]

Movement disorders

While tiapride preferentially targets the limbic system over the striatum, its moderate antagonistic effect on striatal dopamine receptors makes it effective in treating motor deficits that involve this area, such as tardive dyskinesia and chorea. Tiapride's moderate efficacy at D2 receptors [6] may explain why it is able to treat motor symptoms without the extrapyramidal symptoms caused by excess dopamine blockage, which are sometimes seen in haloperidol or chlorpromazine. One clinical study of patients with tardive dyskinesia associated with Parkinson's disease found that tiapride significantly improved motor abilities without affecting other parkinsonian symptoms. [7]

Side effects

Although it is considered a "safe" medicine, it is, like sulpiride, strictly contraindicated for patients under the age of 18 due to its effects during the process of puberty. This is likely related to its side effects on levels of the hormone prolactin, which is involved in sexual development. [8] There are also insufficient clinical data on the other side effects in adolescents.

Tiapride has been found to cause excess prolactin levels in plasma, [7] which can cause decreased libido, infertility and increased risk of breast cancer. [9] This is because dopamine plays a primary role in regulating prolactin release by binding to D2 receptors on prolactin-secreting cells in the anterior pituitary. [10] Thus, when tiapride blocks these receptors these cells are disinhibited and release more prolactin.

The side-effect reported most commonly to the U.S. Food and Drug Administration (FDA) is rhabdomyolysis, a condition characterized by muscle tissue breakdown. [11] Cardiac abnormalities such as prolongation of the QT interval and torsades de pointes have also been observed. [9]

Dosages above approximately 300 mg/day risk inducing tardive dyskinesia. [4] However, given the drug's fairly wide window of tolerable doses, [2] dosages can often be titrated to obtain the desired effect without bringing about motor deficits. In general, tiapride is considered an atypical antipsychotic because of its low risk for extrapyramidal symptoms, such as akinesia and akathisia. These effects are thought to be reduced in tiapride relative to typical antipsychotics because of its selectivity for the limbic system over extrapyramidal areas that control movement. [2]

Pharmacodynamics

Tiapride is a dopamine D2 and D3 receptor antagonist. It is more selective than other neuroleptic drugs such as haloperidol and risperidone, which not only target four of the five known dopamine receptor subtypes (D1-4), but also block serotonin (5-HT2A, 2C), α1- and α2-adrenergic, and histamine H1 receptors. [2] Compared to these drugs, tiapride has a relatively moderate affinity for its target receptors, displacing 50 percent of 3H-raclopride binding at a concentration of 320 nM at D2 receptors and a concentration of 180 nM at D3 receptors.

Tiapride displays a relatively high regional selectivity for limbic areas. One study found that, in contrast with haloperidol, which displays equal affinity for receptors in the rat limbic system and striatum, tiapride shows over three times as much affinity for limbic areas than striatal areas. [2] Another study in rats found tiapride's affinity for the septum, a limbic region, to be over thirty times as high as for the striatum. [12]

Efficacy at the D2 receptor is moderate, with 80 percent of receptors occupied even in the presence of excess tiapride concentrations. [6]

Pharmacokinetics

Tiapride is primarily taken orally in the form of a tablet, but can also be administered via intravenous or intramuscular injection. [4] A liquid oral formulation is also available for elderly patients with difficulty chewing solids. [13] For all three methods of administration, the bioavailability of tiapride is approximately 75 percent. Peak plasma concentrations are attained between 0.4 and 1.5 hours following administration, and steady-state concentrations achieved 24 to 48 hours after beginning administration 3 times a day. It distributes rapidly and exhibits virtually no binding to plasma proteins, giving it a relatively high volume of distribution. Benzamide and its derivatives are highly water-soluble, and because of their polarity are believed to cross the blood–brain barrier via carrier-mediated transport. [14] Elimination of tiapride, mostly in its original form, occurs through renal excretion with a half-life of 3 to 4 hours. [4]

Recommended dosages of tiapride vary with clinical symptoms. In alcoholic patients, delirium or pre-delirium associated with alcohol withdrawal can be alleviated by administration of 400–1200 mg/day or up to 1800 mg/day if necessary. Tremors and other dyskinsias can be treated with 300–800 mg/day. For reducing agitation and aggression in elderly patients, 200–300 mg/day is recommended. [4]

Availability

Tiapride is marketed under various trade names and is widely available outside of the United States. The most common trade name for tiapride is Tiapridal, which is used throughout Europe, Russia, as well as parts of South America, the Middle East, and North Africa. It is also sold under different names in Italy (Italprid, Sereprile), Japan (Tialaread, Tiaryl, Tiaprim, Tiaprizal), Chile (Sereprid), Germany (Tiaprid, Tiapridex), and China (Tiapride). [15]

See also

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">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 for 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">Pimozide</span> Chemical compound

Pimozide is a neuroleptic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine. On a weight basis it is even more potent than haloperidol. It also has special indication for Tourette syndrome and resistant tics.

<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">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<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, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.

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

Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic 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.

Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia, akathisia, parkinsonism characteristic symptoms such as rigidity, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.

<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">Zuclopenthixol</span> Typical antipsychotic medication

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

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

Nemonapride, also previously known as emonapride and sold under the brand name Emilace, is an atypical antipsychotic which is used in the treatment of schizophrenia. It is taken by mouth.

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

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

<span class="mw-page-title-main">Piquindone</span> Chemical compound

Piquindone (Ro 22-1319) is an atypical antipsychotic with a tricyclic structure that was developed in the 1980s but was never marketed. It acts as a selective D2 receptor antagonist, though based on its effects profile its selectivity may be considered controversial. Unlike most other D2 receptor ligands, piquindone displays Na+-dependent binding, a property it shares with tropapride, zetidoline, and metoclopramide.

<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.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

References

  1. ↑ Anvisa (2023-03-31). "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 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
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  5. ↑ Robert PH, Allain H (January 2001). "Clinical management of agitation in the elderly with tiapride". European Psychiatry. 16 (Suppl 1): 42s–47s. doi:10.1016/s0924-9338(00)00527-7. PMID   11520478. S2CID   45212014.
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  8. ↑ Sanford LM, Baker SJ (January 2010). "Prolactin regulation of testosterone secretion and testes growth in DLS rams at the onset of seasonal testicular recrudescence". Reproduction. 139 (1): 197–207. doi: 10.1530/REP-09-0180 . PMID   19755483.
  9. 1 2 Tiefenbacher AE (2006). Tiacob: Summary of Product Characteristics.
  10. ↑ Fitzgerald P, Dinan TG (March 2008). "Prolactin and dopamine: what is the connection? A review article". Journal of Psychopharmacology. 22 (2 Suppl): 12–9. doi:10.1177/0269216307087148. PMID   18477617. S2CID   1326317.
  11. ↑ "Tiapride Hydrochloride". DrugCite. Retrieved 30 October 2012.
  12. ↑ Bischoff S, Bittiger H, Delini-Stula A, Ortmann R (April 1982). "Septo-hippocampal system: target for substituted benzamides". European Journal of Pharmacology. 79 (3–4): 225–32. doi:10.1016/0014-2999(82)90628-8. PMID   7201401.
  13. ↑ Canal M, Desanti CR, Santoni JP (1998). "A new oral formulation of tiapride (drops): pharmacokinetic profile and therapeutic applications". Clinical Drug Investigation. 15 (5): 455–60. doi:10.2165/00044011-199815050-00010. PMID   18370501. S2CID   31687232.
  14. ↑ Härtter S, Hüwel S, Lohmann T, Abou El Ela A, Langguth P, Hiemke C, Galla HJ (November 2003). "How does the benzamide antipsychotic amisulpride get into the brain?--An in vitro approach comparing amisulpride with clozapine". Neuropsychopharmacology. 28 (11): 1916–22. doi: 10.1038/sj.npp.1300244 . PMID   12865899.
  15. ↑ "Tiapride Generic". Generic Drugs. Retrieved 30 October 2012.[ permanent dead link ]
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