Department of Biomedical Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Parkinsons Dis. 2012;2012:489853. doi: 10.1155/2012/489853. Epub 2012 Jun 17.
Dyskinesia, a major complication of treatment of Parkinson's disease (PD), involves two phases: induction, which is responsible for dyskinesia onset, and expression, which underlies its clinical manifestation. The unique cellular and regional distribution of adenosine A(2A) receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned A(2A) receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of A(2A) receptors and the effects of adenosine A(2A) antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant biomarker studies. We also review clinical trials of A(2A) antagonists as adjuncts to L-DOPA in PD patients with motor fluctuations. These studies have generally demonstrated that the addition of an A(2A) antagonist to a stable L-DOPA regimen reduces OFF time and mildly increases dyskinesia. However, limited clinical data suggest that the addition of an A(2A) antagonist along with a reduction of L-DOPA might maintain anti-Parkinsonian benefit and reduce dyskinesia. Whether A(2A) antagonists might reduce the development of dyskinesia has not yet been tested clinically.
运动障碍是帕金森病（PD）治疗的主要并发症，它涉及两个阶段：诱导期，负责运动障碍的发生；表现期，为其临床表现提供基础。由于富含多巴胺的基底神经节区域中的腺苷 A(2A)受体具有独特的细胞和区域分布，并且它们对多巴胺受体刺激具有拮抗作用，因此 A(2A)受体拮抗剂已成为一种有吸引力的非多巴胺能靶点，可改善 PD 特征性的运动障碍。在本文中，我们描述了 A(2A)受体的生化特征，以及在 PD 啮齿动物和灵长类动物模型中，腺苷 A(2A)拮抗剂对 L-DOPA 诱导的运动障碍的影响，以及相关的生物标志物研究。我们还回顾了 A(2A)拮抗剂作为 PD 患者运动波动的 L-DOPA 辅助治疗的临床试验。这些研究普遍表明，在稳定的 L-DOPA 治疗方案中添加 A(2A)拮抗剂可减少 OFF 时间，并轻度增加运动障碍。然而，有限的临床数据表明，添加 A(2A)拮抗剂并减少 L-DOPA 可能会保持抗帕金森病的益处并减少运动障碍。A(2A)拮抗剂是否可能减少运动障碍的发展尚未在临床上进行测试。
