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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/21 22:42:55」(JST)

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Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. On August 15, 2008 the U.S. Food and Drug Administration (FDA) approved the use of tetrabenazine to treat chorea associated with Huntington's disease (HD), the first in the US.^[1] The compound has been known since the 1950s. The effort for US FDA approval was led by Dr. Joseph Jankovic. According to a 2008 news report^[2], "Americans with Huntington's who weren't Jankovic's patients ordered tetrabenazine from Canada if they could afford it. But the worsening exchange rate put the price out of reach for many. A recent check found Canadian Internet pharmacies selling generic 25-milligram pills for $1.75 or more each in U.S. currency, brand-name 25-mg pills for around $2.35 each." After the FDA approval, Dr. Jancovic said "I'm worried that the drug is just going to be too expensive" and initial pricing was $68.50 per 25 mg tablet.^[3]

Pharmacology

Tetrabenazine works mainly as a VMAT-inhibitor^[4] and as such promotes the early metabolic degradation of monoamines, in particular the neurotransmitter dopamine.

Uses

Tetrabenazine is used as a treatment, but not a cure for hyperkinetic disorders^[5]^[6] such as:

Huntington's Disease – specificially the chorea associated with it
Tourette syndrome and other tic disorders
Tardive dyskinesia,^[7] a serious and sometimes irreversible side effect of long-term use of many antipsychotics, mainly typical antipsychotics
Hemiballismus, spontaneous flinging limb movements due to contra-lateral subthalamic nucleus damage

Side effects

Because tetrabenazine is closely related to antipsychotics, many of its side effects are similar. Some of these include:^[8]

Akathisia (aka "restless pacing" – an inability to keep still, with intense anxiety when forced to do so)
Depression - the most common side effect, reported in roughly 15% of those who take the medication
Dizziness, drowsiness, insomnia, fatigue, nervousness and anxiety
Parkinsonism

Unlike many antipsychotics, tetrabenazine is not known to cause tardive dyskinesia.

Warnings

Because of the relatively high incidence of depression, it has been recommended that people with a history of depression avoid taking tetrabenazine.
The concomitant intake of MAO inhibitors is contraindicated.

References

^ 1st US drug for Huntington's disease wins approval
^ Doctor spent decades getting tetrabenazine to market
^ Specialty TrendsRx Availability Alert:Xenazine® (tetrabenazine)
^ Zheng G, Dwoskin LP, Crooks PA (2006). "Vesicular monoamine transporter 2: role as a novel target for drug development". AAPS J 8 (4): E682–92. doi:10.1208/aapsj080478. PMC 2751365. PMID 17233532. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2751365/.
^ Jankovic J, Beach J (1997). "Long-term effects of tetrabenazine in hyperkinetic movement disorders". Neurology 48 (2): 358–62. PMID 9040721.
^ Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Mov. Disord. 22 (2): 193–7. doi:10.1002/mds.21222. PMID 17133512.
^ Ondo WG, Hanna PA, Jankovic J (August 1999). "Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol". Am J Psychiatry 156 (8): 1279–81. PMID 10450276. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=10450276.
^ Robertson MM (March 2000). "Tourette syndrome, associated conditions and the complexities of treatment". Brain. 123 123 (3): 425–62. doi:10.1093/brain/123.3.425. PMID 10686169. http://brain.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10686169.

External links

NIMH Repository data sheet
"Tetrabenazine" from HOPES: Huntington's Disease Outreach Project for Education at Stanford
Detailed monograph on tetrabenazine on rxmed.com
Information on tetrabenazine from netdoctor.co.uk

UpToDate Contents

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1. ハンチントン病：管理 huntington disease management
2. ジストニアの治療 treatment of dystonia
3. 遅発性ジスキネジア：予防および治療 tardive dyskinesia prevention and treatment
4. トゥレット症候群 tourette syndrome
5. 小児における運動減少性運動障害 bradykinetic movement disorders in children

English Journal

Liquid chromatography-tandem mass spectrometric assay for the determination of tetrabenazine and its active metabolites in human plasma: a pharmacokinetic study.

Derangula VR, Pilli NR, Nadavala SK, Adireddy V, Inamadugu JK, Ponneri V.SourceResearch Studies, Rayalaseema University, Kurnool-, 518 002, India; Wellquest Clinical Research Laboratories, Ramanthapur, Hyderabad, 500 013, India.
Biomedical chromatography : BMC.Biomed Chromatogr.2013 Jun;27(6):792-801. doi: 10.1002/bmc.2862. Epub 2013 Jan 21.
A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for the simultaneous quantification of tetrabenazine and its active metabolites α-dihydrotetrabenazine and β-dihydrotetrabenazine in human plasma. Tetrabenaz
PMID 23339053

Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models.

Schäfer MK, Hartwig NR, Kalmbach N, Klietz M, Anlauf M, Eiden LE, Weihe E.SourceDepartment of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University Marburg, Robert-Koch-Straße 8, 35037, Marburg, Germany, mkh.schafer@staff.uni-marburg.de.
Diabetologia.Diabetologia.2013 May;56(5):1047-56. doi: 10.1007/s00125-013-2847-7. Epub 2013 Feb 13.
AIMS/HYPOTHESIS: Imaging of beta cell mass (BCM) is a major challenge in diabetes research. The vesicular monoamine transporter 2 (VMAT2) is abundantly expressed in human beta cells. Radiolabelled analogues of tetrabenazine (TBZ; a low-molecular-weight, cell-permeant VMAT2-selective ligand) have bee
PMID 23404442

Japanese Journal

前シナプス神経サイトプラズマにおけるドパミン枯渇薬テトラベナジンを利用した各種薬物の移所運動促進機序の分類

栗原久
日米高齢者保健福祉学会誌 (2), 61-70, 2007-03-00
NAID 40015512581

<原著>テトラベナジン反復投与によるラット黒質線条体の組織形態計測学的解析 : 実験的パーキンソン病モデルへの応用をめざして

伊藤龍生,林義之,佐藤隆夫
近畿大学医学雑誌 26(3), 153-169, 2001-11-25
… Tetrabenazine(TBZ)は神経細胞内でカテコールアミン(CA)の枯渇をもたらすことから舞踏病の治療薬として1950年代より使用されてきた.現在は, ラットへの単回投与によりうつ病のモデルとして用いられる.TBZは神経終末におけるシナプス小胞膜上に存在するvesicular monoamine transporterの阻害により, CAのシナプス小胞内への取り込みを阻害する.CAの1つであるドーパミン(DA)の異常がパーキンソン病(PD)で認められることは広く知られて …
NAID 110000061785

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リンク元

「テトラベナジン」

Tetrabenazine
Systematic (IUPAC) name
	(SS,RR)-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-pyrido[2,1-a]isoquinolin-2-one
Clinical data
Trade names	Xenazine
AHFS/Drugs.com	Consumer Drug Information
Pregnancy cat.	C
Legal status	℞-only (US)
Routes	Oral (tablets, 25 mg)
Pharmacokinetic data
Bioavailability	Low, extensive first pass effect
Protein binding	82–85%
Metabolism	Hepatic (CYP2D6-mediated)
Excretion	Renal and fecal
Identifiers
CAS number	58-46-8
ATC code	N07XX06
PubChem	CID 6018
DrugBank	DB04844
ChemSpider	5796
UNII	Z9O08YRN8O
KEGG	D08575
ChEMBL	CHEMBL117785
Synonyms	Ro-1-9569
Chemical data
Formula	C19H27NO3
Mol. mass	317.427 g/mol
	SMILES O=C3C(CC(C)C)CN2C(c1c(cc(OC)c(OC)c1)CC2)C3;
	InChI InChI=1S/C19H27NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16H,5-7,10-11H2,1-4H3 ; Key:MKJIEFSOBYUXJB-UHFFFAOYSA-N ;
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　　[★]

英: tetrabenazine
商: コレアジン
関: ハンチントン病

ハンチントン病の治療薬。
日本では承認されていない。

参考

1.

http://aoyamapharmacy.health.officelive.com/aoyamapharmacyhealthofficeliveFDAcom.aspx

2.

http://www.mhlw.go.jp/shingi/2008/12/dl/s1224-5b.pdf

[0] 1st US drug for Huntington's disease wins approval

[1] Doctor spent decades getting tetrabenazine to market

[2] Specialty TrendsRx Availability Alert:Xenazine® (tetrabenazine)

[GZ_2006-3] Zheng G, Dwoskin LP, Crooks PA (2006). "Vesicular monoamine transporter 2: role as a novel target for drug development". AAPS J 8 (4): E682–92. doi:10.1208/aapsj080478. PMC 2751365. PMID 17233532. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2751365/.

[JankovicHyperkinectic-4] Jankovic J, Beach J (1997). "Long-term effects of tetrabenazine in hyperkinetic movement disorders". Neurology 48 (2): 358–62. PMID 9040721.

[pmid17133512-5] Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Mov. Disord. 22 (2): 193–7. doi:10.1002/mds.21222. PMID 17133512.

[pmid10450276-6] Ondo WG, Hanna PA, Jankovic J (August 1999). "Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol". Am J Psychiatry 156 (8): 1279–81. PMID 10450276. http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=10450276.

[7] Robertson MM (March 2000). "Tourette syndrome, associated conditions and the complexities of treatment". Brain. 123 123 (3): 425–62. doi:10.1093/brain/123.3.425. PMID 10686169. http://brain.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10686169.

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tetrabenazine