Baylor College of Medicine, Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Houston, TX, USA.
Expert Rev Neurother. 2011 Nov;11(11):1509-23. doi: 10.1586/ern.11.149.
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.
四苯嗪（TBZ；Xenazine）是一种有效的、选择性的、可逆的单胺神经末梢耗竭剂。TBZ 抑制囊泡单胺转运体 2，而在人类中，这种转运体几乎只在大脑中表达。TBZ 在肝脏中被羰基还原酶迅速代谢为氢四苯嗪的立体异构体，其中一些是囊泡单胺转运体 2 的有效抑制剂。TBZ 最初在 20 世纪 50 年代被开发用于治疗精神分裂症，自 20 世纪 70 年代以来，有几项出版物报道了 TBZ 在治疗各种运动障碍中的疗效。虽然 TBZ 对控制不自主运动非常有效，但最佳剂量存在相当大的个体差异，最佳剂量被定义为研究者认为能以最小或可耐受的不良反应提供最大疗效的剂量。这种可变性部分归因于目标症状的严重程度和机制的差异，以及代谢 TBZ 为其活性代谢物的羰基还原酶的活性差异。主要包括镇静、帕金森病、静坐不能和抑郁在内的剂量限制不良事件通常在减少剂量后迅速逆转。除了在亨廷顿病中已确立的抗舞蹈病疗效外，该药物还被报道对其他各种运动障碍有效，包括迟发性运动障碍和与妥瑞氏症相关的抽动。
