Introduction

Prolonged treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of uncontrolled movements (L-DOPA-induced dyskinesias (LID)) in Parkinson’s disease (PD). There is currently only a single approved drug for the treatment of LID, a long-acting preparation of the NMDA antagonist, amantadine, that has variable benefits and side-effects. Therefore, new treatments for LID remain an unmet in PD.

Areas covered

We review the current strategies for the management of LID; the pathogenic mechanisms underlying the development of LID, which provides the rationale for clinical trials of novel targets for LID and provide a review of phase II/III trials for emerging drugs for LID, with either positive results, or ongoing studies, reported between January 2014 and December 2019.

Expert opinion

There are several ongoing studies for agents that showed possible benefit at phase Ib/IIa for reducing LID. However, there are no new positive phase III double-blind randomized controlled clinical trials (DBRCT) for emerging treatments for LID. Generating better preclinical models, more precise recruitment tools and better outcome measures remain a priority. The pharmacology of drugs investigated for LID may be too selective; therefore, evaluating combinations of drugs is worthy of consideration as is the repurposing of existing drugs with multiple pharmacological targets.

中文翻译：

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用于治疗L-DOPA引起的运动障碍的新兴药物：更新。

介绍

长期使用L-3,4-二羟基苯丙氨酸（L-DOPA）治疗会导致帕金森氏病（PD）发生不受控制的运动（L-DOPA引起的运动障碍（LID））。目前，只有一种经批准的药物可治疗LID，这是NMDA拮抗剂金刚烷胺的长效制剂，具有不同的益处和副作用。因此，PD的LID的新疗法仍未得到满足。

覆盖区域

我们回顾了当前的LID管理策略；LID发生的潜在致病机制，该研究为LID新靶标的临床试验提供了理论依据，并对LID新兴药物的II / III期试验进行了回顾，无论是阳性结果还是正在进行的研究，均报告于2014年1月之间和2019年12月。

专家意见

正在进行的针对药剂的研究表明，在Ib / IIa阶段降低LID可能具有益处。但是，目前还没有新的III期阳性双盲随机对照临床试验（DBRCT）用于新兴的LID治疗。产生更好的临床前模型，更精确的募集工具和更好的结果指标仍然是优先事项。对LID进行研究的药物的药理学可能选择性太高。因此，评估药物组合是值得考虑的，就像重新使用具有多种药理学目标的现有药物一样。