tiapride

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tiapride hydrochloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/15 20:45:02」(JST)

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Tiapride
Molecular structure
3D molecular structure
IUPAC name N-(2-Diethylaminoethyl)-2-methoxy-5-methylsulfonylbenzamide
Identifiers
CAS number	51012-32-9 N
PubChem	5467
ChemSpider	5268 Y
KEGG	D08590 Y
MeSH	Tiapride
ChEMBL	CHEMBL84158 Y
ATC code	N05AL03
Jmol-3D images	Image 1
SMILES O=S(=O)(c1ccc(OC)c(C(=O)NCCN(CC)CC)c1)C
InChI InChI=1S/C15H24N2O4S/c1-5-17(6-2)10-9-16-15(18)13-11-12(22(4,19)20)7-8-14(13)21-3/h7-8,11H,5-6,9-10H2,1-4H3,(H,16,18) Y Key: JTVPZMFULRWINT-UHFFFAOYSA-N Y InChI=1/C15H24N2O4S/c1-5-17(6-2)10-9-16-15(18)13-11-12(22(4,19)20)7-8-14(13)21-3/h7-8,11H,5-6,9-10H2,1-4H3,(H,16,18) Key: JTVPZMFULRWINT-UHFFFAOYAN
Properties
Molecular formula	C15H24N2O4S
Molar mass	328.42706
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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. 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.

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 (D_1-4), but also block serotonin (5-HT_{2A, 2C}), α₁- and α₂-adrenergic, and histamine H1 receptors. 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. 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.

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

Pharmacokinetics

Tiapride is primarily taken orally in the form of a tablet, but can also be administered via intravenous or intramuscular injection. A liquid oral formulation is also available for elderly patients with difficulty chewing solids. 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. Elimination of tiapride, mostly in its original form, occurs through renal excretion with a half-life of 3 to 4 hours.

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.

Treatment

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 antidopamingergic effects are the most likely mechanism for its clinical efficacy, although others believe some other mechanism might be involved. Alcoholic patients treated with tiapride at a dosage of 300 mg/day reported reduced psychological distress and improved abstinence from alcohol. In another study in which alcoholic patients were given titrated doses up to 800 mg/day, subjects showed significant improvements in ratigns of withdrawal, craving, psychiatric symptoms and quality of life.

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. This sets it apart from the benzodiazepines, which are contraindicated with alcohol and can be addictive. Moreover, tiapride's rapid onset makes intravenous or intramuscular injection prior to or during withdrawal episodes particularly effective.

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.

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.

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 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.

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^{[citation needed]}. This is likely related to its side effects on levels of the hormone prolactin, which is involved in sexual development. There are also insufficient clinical data on the other side effects in adolescents.

Tiapride has been found to cause excess prolactin levels in plasma, which can cause decreased libido, infertility and increased risk of breast cancer. 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. 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. Cardiac abnormalities such as prolongation of the QT interval and torsades de pointes have also been observed.

Dosages above approximately 300 mg/day risk inducing tardive dyskinesia. However, given the drug's fairly wide window of tolerable doses, 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 akathesia. 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.

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 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).

See also

• Amisulpride
• Nemonapride
• Remoxipride
• Sulpiride
• Sultopride

References

UpToDate Contents

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• 1. 神経有棘赤血球症 neuroacanthocytosis

English Journal

• The D2/D3-receptor antagonist tiapride impairs concurrent but not sequential taste aversion learning.

• Mediavilla C, Mahía J, Bernal A, Puerto A.SourcePsychobiology, University of Granada, Campus Cartuja, 18071 Granada, Spain. cristina@ugr.es
• Brain research bulletin.Brain Res Bull.2012 Feb 10;87(2-3):346-9. Epub 2011 Nov 9.
• Taste aversion learning (TAL) is a learning modality in which the animals reject a gustatory stimulus associated with the administration of noxious visceral substances. This learning can be established by concurrent or sequential procedures that involve different anatomical and functional mechanisms
• PMID 22085742

• High-performance liquid chromatographic determination of tiapride and its phase I metabolite in blood plasma using tandem UV photodiode-array and fluorescence detection.

• Nobilis M, Vybíralová Z, Szotáková B, Sládková K, Kuneš M, Svoboda Z.SourceInstitute of Experimental Biopharmaceutics, Joint Research Center of PROMEDCS Praha as and Academy of Sciences of the Czech Republic, Hradec Králové, Czech Republic. nobilis@uebf.cas.cz
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.J Chromatogr B Analyt Technol Biomed Life Sci.2011 Dec 15;879(32):3845-52. Epub 2011 Nov 3.
• New bioanalytical SPE-HPLC-PDA-FL method for the determination of the neuroleptic drug tiapride and its N-desethyl metabolite was developed, validated and applied to xenobiochemical and pharmacokinetic studies in humans and animals. The sample preparation process involved solid-phase extraction of d
• PMID 22100559

Japanese Journal

• 高齢者における副作用(転倒・骨折・誤嚥) (特集 向精神薬の副作用と対策 Update)

• 渡辺 誠,土谷 昌広,工藤 久 [他]
• 臨床精神医学 43(11), 1633-1639, 2014-11
• NAID 40020246539

• Neuroleptic Malignant Syndrome Induced by Combination Therapy with Tetrabenazine and Tiapride in a Japanese Patient with Huntington's Disease at the Terminal Stage of Recurrent Breast Cancer

• Nozaki Ichiro,Furukawa Yutaka,Kato-Motozaki Yuko,Ikeda Tokuhei,Tagami Atsuro,Takahashi Kazuya,Ishida Chiho,Komai Kiyonobu
• Internal Medicine 53(11), 1201-1204, 2014
• … We herein describe the case of an 81-year-old Japanese woman with neuroleptic malignant syndrome that occurred 36 days after the initiation of combination therapy with tiapride (75 mg/day) and tetrabenazine (12.5 mg/day) for Huntington's disease. … The patient had been treated with tiapride or tetrabenazine alone without any adverse effects before the administration of the combination therapy. …
• NAID 130004466330

• Differential Pulse Anodic Voltammetric Determination of Tiapride Hydrochloride in Pharmaceutical Preparation and Human Urine Using Carbon Paste Electrodes

• Zayed S. I. M.
• Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 27(5), 535-539, 2011-05-10
• NAID 10028288847

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チアプリド塩酸塩(Tiapride hydrochloride)の検索ならお薬検索QLife（キューライフ）。お医者さんが処方する処方薬と、薬局で買える市販薬(OTC)、の効果と副作用、写真、添付文書、保管方法等を掲載。商品名だけでなく一般名や剤形 ...

• Tiapride - Springer

Synopsis Tiapride is a substituted benzamide derivative with selective dopamine D 2-receptor antagonist properties which appears to have preferential affinity for extrastriatal dopamine receptors. Animal and clinical studies show that ...

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