University Health Network, Toronto Western Research Institute, Toronto M5T 2S8, Ontario, Canada.
Int Rev Neurobiol. 2011;98:123-50. doi: 10.1016/B978-0-12-381328-2.00005-5.
L-DOPA-induced dyskinesia (LID) is a major complication of the treatment of Parkinson's disease (PD). LID comprises two major components, the priming process responsible for its onset and the expression of involuntary movements that underlies its clinical manifestation. The mechanisms responsible for these components are partially understood and their biochemical basis is being unraveled but avoidance and treatment remain an issue. In this chapter, we review what is known about the involvement of dopaminergic systems in LID and the way in which dopaminergic therapy can be used to avoid the onset of LID or to reverse or suppress involuntary movements once these have been established. The involvement of specific dopamine receptor subtypes, continuous dopaminergic stimulation (CDS) and continuous drug delivery (CDD) is reviewed. However, a major role is emerging in the avoidance and suppression of LID through the use of nondopaminergic mechanisms and we consider the present and future use of glutamatergic drugs, serotoninergic agents, adenosine antagonists and others as a means of improving therapy. There is compelling basic science supporting a role for nondopaminergic approaches to LID but at the moment the translational benefit to PD is not being achieved as predicted. There needs to be further consideration of why this is the case and how in future, both experimental models of dyskinesia and clinical trial design can be optimized to ensure success.
左旋多巴诱导的运动障碍（LID）是帕金森病（PD）治疗的主要并发症。LID 由两个主要组成部分组成，负责其发病的启动过程和构成其临床表现的不自主运动的表达。这些组成部分的机制部分得到了理解，其生化基础正在被揭示，但避免和治疗仍然是一个问题。在这一章中，我们回顾了已知的与多巴胺能系统在 LID 中的参与以及多巴胺能治疗如何被用来避免 LID 的发作或在已经建立的情况下逆转或抑制不自主运动的方式。我们回顾了特定多巴胺受体亚型、持续多巴胺刺激（CDS）和持续药物输送（CDD）的参与。然而，通过使用非多巴胺能机制，在避免和抑制 LID 方面出现了一个主要作用，我们考虑了目前和未来使用谷氨酸能药物、血清素能药物、腺苷拮抗剂等作为改善治疗的手段。有强有力的基础科学支持非多巴胺能方法在 LID 中的作用，但目前对 PD 的转化效益并没有像预期的那样实现。需要进一步考虑为什么会这样，以及在未来，如何优化运动障碍的实验模型和临床试验设计，以确保成功。
