Tetrabenazine is a drug for the symptomatic treatment of

hyperkinetic Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. Hyperkinesia is a state of excessive restlessness which is featured in a large variet ...

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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved the use of tetrabenazine to treat

chorea Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived from the grc, χορεία ("dance"; see choreia), as the quick movem ...

associated with

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

. Although other drugs had been used "

off label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although m ...

," tetrabenazine was the first approved treatment for Huntington's disease in the U.S.1st US drug for Huntington's disease wins approval
The compound has been known since the 1950s.

Medical uses

Tetrabenazine is used as a treatment, but not as a

cure A cure is a substance or procedure that ends a medical condition, such as a medication, a surgical operation, a change in lifestyle or even a philosophical mindset that helps end a person's sufferings; or the state of being healed, or cured. The ...

, for hyperkinetic disorders such as: *

– specifically, the

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 Hemiballismus or hemiballism is a basal ganglia syndrome resulting from damage to the subthalamic nucleus in the basal ganglia. Hemiballismus is a rare hyperkinetic movement disorder, that is characterized by violent involuntary limb movements, ...

, spontaneous flinging limb movements due to contra-lateral

subthalamic nucleus The subthalamic nucleus (STN) is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. In terms of anatomy, it is the major part of the subthalamus. As suggested by its name, the ...

damage Tetrabenazine has been used as an

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

in the treatment of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

, both in the past and in modern times.

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.

Warnings

There is a

boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that i ...

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

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 Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

, and

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...

from nerve terminals. Tetrabenazine reversibly inhibits

vesicular monoamine transporter 2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...

, resulting in decreased uptake of monoamines into synaptic vesicles, as well as depletion of monoamine storage.

References

External links

Xenazine prescribing information FDANIMH Repository data sheet
from HOPES: Huntington's Disease Outreach Project for Education at Stanford
Detailed monograph on tetrabenazine on rxmed.com
{{Monoamine reuptake inhibitors Anxiogenics Huntington's disease Ketones Orphan drugs Phenol ethers Tardive dyskinesia Tetrahydroisoquinolines VMAT inhibitors