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用于迟发性运动障碍的VMAT2抑制剂——实践意义

VMAT2 Inhibitors for Tardive Dyskinesia-Practice Implications.

作者信息

Peckham Alyssa M, Nicewonder Jessica A

机构信息

1 Department of Pharmacy Practice, Midwestern University College of Pharmacy-Glendale, Glendale, AZ, USA.

2 Midwestern University College of Pharmacy-Glendale, Glendale, AZ, USA.

出版信息

J Pharm Pract. 2019 Aug;32(4):450-457. doi: 10.1177/0897190018756512. Epub 2018 Feb 18.

Abstract

Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively. These agents were pharmacologically modified from tetrabenazine, a VMAT2 inhibitor used off-label in the treatment of tardive dyskinesia. Despite FDA-labeled indications of deutetrabenazine and valbenazine, each agent was explored as a treatment option for those with tardive dyskinesia. In this study, the pharmacologic modifications of the 2 new VMAT2 inhibitors are described, with detailed explanation as to how these may impact clinical practice. The associated case series, observational studies, and clinical trials exploring their use in the treatment of tardive dyskinesia are reported with expert opinion on practice implication.

摘要

迟发性运动障碍是一种潜在不可逆的、使人衰弱的运动亢进性疾病,可能由多巴胺受体拮抗剂引起。症状的及时识别和缓解对于预防疾病的不可逆性至关重要,尽管目前的治疗方案在实现强有力、有效且长期的症状控制方面仍有不足。2017年4月,美国食品药品监督管理局(FDA)批准了2种新的囊泡单胺转运体2(VMAT2)抑制剂,氘代丁苯那嗪和缬苯那嗪,分别用于治疗与亨廷顿舞蹈病相关的舞蹈症和迟发性运动障碍。这些药物是从丁苯那嗪进行药理学改造而来,丁苯那嗪是一种用于治疗迟发性运动障碍的未获FDA批准的VMAT2抑制剂。尽管FDA为氘代丁苯那嗪和缬苯那嗪标注了适应证,但每种药物都被探索作为迟发性运动障碍患者的一种治疗选择。在本研究中,描述了这2种新的VMAT2抑制剂的药理学改造,并详细解释了它们如何可能影响临床实践。报告了探索它们用于治疗迟发性运动障碍的相关病例系列、观察性研究和临床试验,并给出了关于实践意义的专家意见。

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