Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders.
Tetrabenazine (TBZ; Xenazine) is a potent, selective, reversible depletor of monoamines from nerve terminals. TBZ inhibits the vesicular monoamine transporter type 2 which, in humans, is expressed nearly exclusively in the brain. TBZ is rapidly metabolized in the liver by carbonyl reductase to stereoisomers of hydrotetrabenazine, some of which are potent inhibitors of vesicular monoamine transporter type 2. Initially developed in the 1950s for schizophrenia, since the 1970s several publications have reported on the efficacy of TBZ in the treatment of various hyperkinetic movement disorders. Although quite effective in controlling the involuntary movements, there were considerable inter-individual differences in the optimal dose, defined as the dose judged by the investigator to provide the greatest efficacy with minimal or tolerable adverse events. This variability is in part owing to differences in severity and mechanism of the target symptoms and to variable activity of the enzyme carbonyl reductase that metabolizes TBZ to its active metabolites. Dose-limiting adverse events, consisting mainly of sedation, parkinsonism, akathisia and depression, are usually rapidly reversible upon dosage reduction. In addition to its established antichorea efficacy in Huntington's disease, the drug has been reported to also be effective in a variety of other hyperkinetic movement disorders, including tardive dyskinesia and tics associated with Tourette's syndrome.
Baylor College of Medicine, Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Houston, TX, USA. josephj@bcm.tmc.edu
Joseph
J
Jankovic
Kathleen
K
Clarence-Smith
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D002819:Chorea / Q000188:drug therapy*; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy*; D013747:Tetrabenazine / Q000627:therapeutic use*
D018759:Adrenergic Uptake Inhibitors; D013747:Tetrabenazine