Tetrabenazine

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, Nitoman
AHFS/Drugs.com	Consumer Drug Information
Pregnancy category	C
Legal status	℞-only (US)
Routes of administration	Oral (tablets, 12.5 and 25 mg)
Pharmacokinetic data
Bioavailability	Low, extensive first pass effect
Protein binding	82–85%
Metabolism	Hepatic (CYP2D6-mediated)
Excretion	Renal (~75%) and fecal (7–16%)
Identifiers
CAS Number	58-46-8 Y
ATC code	N07XX06 (WHO)
PubChem	CID: 6018
IUPHAR/BPS	4834
DrugBank	DB04844 Y
ChemSpider	5796 Y
UNII	Z9O08YRN8O Y
KEGG	D08575 Y
ChEMBL	CHEMBL117785 Y
Synonyms	Ro-1-9569
Chemical data
Formula	C19H27NO3
Molecular 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 Y Key:MKJIEFSOBYUXJB-UHFFFAOYSA-N Y
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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. The compound has been known since the 1950s.

Pharmacology

The precise mechanism of action of tetrabenazine is unknown. The anti-chorea effect is believed to be related to its effect as a reversible depletory of monoamines (such as dopamine, serotonin, norepinephrine and histamine) from nerve terminals. Tetrabenazine reversibly inhibits VMAT-2 resulting in decreased uptake of monamines into synaptic vesicles as well as depleted monoamine stores.

Uses

Tetrabenazine is used as a treatment, but not as a cure, for hyperkinetic disorders such as:

• Huntington's Disease – specifically the chorea associated with it
• Tourette syndrome and other tic disorders
• Tardive dyskinesia, 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

Most common adverse reactions (>10% and at least 5% greater than placebo) were: sedation/somnolence, fatigue, insomnia, depression, akathisia, anxiety and nausea.

Warnings

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

• 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

External links

• Xenazine prescribing information FDA
• 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