Dorfman Benjamin J, Jimenez-Shahed Joohi
Robert & John M. Bendheim Parkinson & Movement Disorders Center, Department of Neurology, Icahn School of Medicine at Mount Sinai , New York, NY, USA.
Movement Disorders Neuromodulation & Brain Circuit Therapeutics, Departments of Neurology and Neurosurgery, Icahn School of Medicine at Mount Sinai , New York, NY, USA.
Expert Rev Neurother. 2021 Jan;21(1):9-20. doi: 10.1080/14737175.2021.1848548. Epub 2020 Nov 23.
: Tardive dyskinesia (TD) is a hyperkinetic movement disorder that arises as a complication of exposure to dopamine receptor blocking agents. Vesicular monoamine transporter type 2 (VMAT2) inhibitors reduce dyskinesia by decreasing transport of monoamines, including dopamine, into presynaptic vesicles, leaving unpackaged dopamine to be metabolized by monoamine oxidase. Deutetrabenazine was adapted from an earlier VMAT2 inhibitor, tetrabenazine, by substituting three deuterium isotopes in place of three hydrogen isotopes at the site of metabolic degradation to improve upon the pharmacokinetics of the parent compound. : The authors reviewed the pivotal trials examining the safety and efficacy of deutetrabenazine, as well as long-term data from an open-label extension. Also reviewed were posters and oral presentations, as well as information from the product label and the United States Food and Drug Administration. : Deutetrabenazine is effective at decreasing dyskinesia in TD, but drug selection and cost-effectiveness between existing VMAT2 inhibitors are evolving areas of study. Other areas of investigation include novel anti-dyskinetic agents and use of deep brain stimulation.
迟发性运动障碍(TD)是一种运动亢进性疾病,是接触多巴胺受体阻断剂引发的并发症。囊泡单胺转运体2(VMAT2)抑制剂通过减少包括多巴胺在内的单胺向突触前囊泡的转运来减轻运动障碍,使未包装的多巴胺被单胺氧化酶代谢。氘代丁苯那嗪由早期的VMAT2抑制剂丁苯那嗪改良而来,在代谢降解位点用三个氘同位素取代三个氢同位素,以改善母体化合物的药代动力学。作者回顾了检验氘代丁苯那嗪安全性和有效性的关键试验,以及来自开放标签扩展研究的长期数据。还回顾了海报和口头报告,以及产品标签和美国食品药品监督管理局的信息。氘代丁苯那嗪在减轻TD的运动障碍方面有效,但现有VMAT2抑制剂之间的药物选择和成本效益是不断发展的研究领域。其他研究领域包括新型抗运动障碍药物和深部脑刺激的应用。