The dose of XENAZINE should be individualized. The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. XENAZINE should be titrated up slowly at weekly intervals by 12.5 mg, to allow the identification of a dose that reduces chorea and is well tolerated. If a dose of 37.5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg. If adverse events such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety or intolerable sedation occur, titration should be stopped and the dose should be reduced. If the adverse event does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants).

The brains from male SpragueeDawley rats (approximately 200-225 g weight) (Taconic Labs) were removed, placed on ice, and the striatum was rapidly removed and frozen (-80 C). Thereafter, membranes were prepared by homogenizing striatum samples in 20 volumes (w/v) of ice cold HEPES-sucrose buffer (50 mM HEPES, 0.32 M sucrose, pH adjusted to 8.0) using a Brinkman Polytron (setting 6 for 20 s), and centrifuging them at 20,000xg for 10 min at 4 C. The resulting pellet was resuspended in buffer, recentrifuged and again resuspended in buffer to provide a concentration of 10 mg/mL. Ligand binding experiments were conducted in polystyrene assay tubes containing 0.5 mL HEPES-sucrose buffer for 60 min at room temperature. Each tube contained 2 nM [3H]DHTBZ (specific activity 20 Ci/mmol) (American Radiolabeled Chemicals) and 1.0 mg striatal tissue (original wet weight). Nonspecific binding was determined using 20 mkM(+/-)-TBZ (Tetrabenazine) (Sigma Chemical Co., St Louis, MO). Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.5% PEI (polyethyleneimine), using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, MD). These filters were then washed twice with 5 mL cold buffer and placed in scintillation vials. Beckman Ready Safe (3.0 mL) was added and the vials were counted the next day using