Tetrabenazine

Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. 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.

Tetrabenazine
Clinical data
Trade namesXenazine, Xentra, Nitoman, others
Other namesRo-1-9569
AHFS/Drugs.comConsumer Drug Information
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    administration    		By mouth (tablets)
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only
    Pharmacokinetic data
    BioavailabilityLow, extensive first pass effect
    Protein binding82–85%
    MetabolismHepatic (CYP2D6-mediated)
    ExcretionRenal (~75%) and fecal (7–16%)[1]
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.000.348
    Chemical and physical data
    FormulaC19H27NO3
    Molar mass317.427 g/mol g·mol−1
    3D model (JSmol)
    ChiralityRacemic mixture
      (verify)

    Medical uses

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

    Side effects

    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

    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

    Pharmacology

    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 monoamines into synaptic vesicles, as well as depletion of monoamine storage.[1]

    See also

    References
    1. "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
    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. doi:10.1176/ajp.156.8.1279 (inactive 2019-08-20). PMID 10450276.
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