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.