Tetrabenazine
Encyclopedia
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. The effort for US FDA approval was led by Dr. Joseph Jankovic. According to a 2008 news report, "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.
and as such promotes the early metabolic
degradation of monoamines, in particular the neurotransmitter
dopamine
.
for hyperkinetic disorders such as:
Unlike many antipsychotics, tetrabenazine is not known to cause tardive dyskinesia
.
Hyperkinesis
Hyperkinesia, also known as hyperkinesis, refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both...
movement disorder
Movement disorder
Movement disorders include:* Akathisia * Akinesia * Associated Movements * Athetosis...
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
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
. On August 15, 2008 the U.S. Food and Drug Administration (FDA) approved the use of tetrabenazine to treat chorea
Chorea (disease)
Choreia is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term choreia is derived from the Greek word χορεία , see choreia , as the quick movements of the feet or hands are vaguely comparable to dancing or piano playing.The term...
associated with Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
(HD), the first in the US. 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, "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.
Pharmacology
Tetrabenazine works mainly as a VMAT-inhibitorVMAT2
The vesicular monoamine transporter 2 also known as solute carrier family 18 member 2 is a protein that in humans is encoded by the SLC18A2 gene...
and as such promotes the early metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
degradation of monoamines, in particular the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
.
Uses
Tetrabenazine is used as a treatment, but not a cureCure
A cure is a completely effective treatment for a disease.The Cure is an English rock band.Cure, or similar, may also refer to:-Film and television:* The Cure , a short film starring Charlie Chaplin...
for hyperkinetic disorders such as:
- Huntington's DiseaseHuntington's diseaseHuntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
– specificially the chorea associated with it - Tourette syndromeTourette syndromeTourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical tics and at least one vocal tic; these tics characteristically wax and wane...
and other tic disorderTic disorderTic disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders based on type and duration of tics...
s - Tardive dyskinesiaTardive dyskinesiaTardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, a serious and sometimes irreversible side effect of long-term use of many antipsychotics, mainly typical antipsychoticTypical antipsychoticTypical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
s - HemiballismusHemiballismusHemiballismus is a very rare movement disorder. It is 500 times rarer than Parkinson's disease. Its effects can sometimes be severe enough to prevent patients from being able to perform daily functions. It is usually associated with structural brain lesions but can occur with metabolic abnormalities...
, spontaneous flinging limb movements due to contra-lateral subthalamic nucleusSubthalamic nucleusThe subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
damage
Side effects
Because tetrabenazine is closely related to antipsychotics, many of its side effects are similar. Some of these include:- AkathisiaAkathisiaAkathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
(aka "restless pacing" – an inability to keep still, with intense anxiety when forced to do so) - DepressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
- the most common side effect, reported in roughly 15% of those who take the medication - DizzinessDizzinessDizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, drowsiness, insomnia, fatigue, nervousness and anxiety - ParkinsonismParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
Unlike many antipsychotics, tetrabenazine is not known to cause tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
.
Warnings
- Because of the relatively high incidence of depressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, it has been recommended that people with a history of depression avoid taking tetrabenazine. - The concomitant intake of MAO inhibitors is contraindicatedContraindicationIn medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
.
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