Tetrabenazine

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Tetrabenazine
Tetrabenazine.svg
Tetrabenazine3d.png
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, Nitoman
AHFS/Drugs.com Consumer Drug Information
Pregnancy
category
  • C
Routes of
administration
Oral (tablets, 12.5 and 25 mg)
Legal status
Legal status
  • ℞-only (US)
Pharmacokinetic data
Bioavailability Low, extensive first pass effect
Protein binding 82–85%
Metabolism Hepatic (CYP2D6-mediated)
Excretion Renal (~75%) and fecal (7–16%)[1]
Identifiers
CAS Number 58-46-8 YesY
ATC code N07XX06 (WHO)
PubChem CID 6018
IUPHAR/BPS 4834
DrugBank DB04844 YesY
ChemSpider 5796 YesY
UNII Z9O08YRN8O YesY
KEGG D08575 YesY
ChEMBL CHEMBL117785 YesY
Synonyms Ro-1-9569
Chemical data
Formula C19H27NO3
Molar mass 317.427 g/mol
Chirality Racemic mixture
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Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is available as Xenazine in the United States as an orphan drug. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenazine to treat chorea associated with Huntington's disease. Although other drugs had been used "off label," tetrabenazine was the first approved treatment for Huntington's disease in the U.S.[2] The compound has been known since the 1950s.

Pharmacology[edit]

The precise mechanism of action of tetrabenazine is unknown. Its anti-chorea effect is believed to be due to a reversible depletion of monoamines such as dopamine, serotonin, norepinephrine, and histamine from nerve terminals. Tetrabenazine reversibly inhibits vesicular monoamine transporter 2, resulting in decreased uptake of monamines into synaptic vesicles, as well as depletion of monoamine storage.[1]

Uses[edit]

Tetrabenazine is used as a treatment, but not as a cure, for hyperkinetic disorders[3][4] such as:

Side effects[edit]

The most common adverse reactions, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts, akathisia, anxiety and nausea.[1]

Warnings[edit]

There is a boxed warning associated with the use of tetrabenazine:[1]

  • Increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease
  • Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of tetrabenazine
  • Monitor patients for emergence or worsening of depression, suicidality or unusual changes in behavior
  • Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviours of concern promptly to the treating physician
  • Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation
  • Tetrabenazine is contraindicated in patients who are actively suicidal and in patients with untreated or inadequately treated depression

References[edit]

  1. ^ a b c d "Xenazine (tetrabenazine) Tablets, for Oral Use. Full Prescribing Information. Revised: 6/2015" (PDF). H. Lundbeck A/S. Retrieved 9 December 2015. 
  2. ^ 1st US drug for Huntington's disease wins approval[dead link]
  3. ^ Jankovic J, Beach J (1997). "Long-term effects of tetrabenazine in hyperkinetic movement disorders". Neurology 48 (2): 358–62. doi:10.1212/wnl.48.2.358. PMID 9040721. 
  4. ^ Kenney C, Hunter C, Jankovic J (January 2007). "Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders". Movement Disorders 22 (2): 193–7. doi:10.1002/mds.21222. PMID 17133512. 
  5. ^ Ondo WG, Hanna PA, Jankovic J (August 1999). "Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol". American Journal of Psychiatry 156 (8): 1279–81. PMID 10450276. 

External links[edit]