Albert Szent-Györgyi Clinical Center, Department of Neurology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Expert Opin Drug Metab Toxicol. 2011 Apr;7(4):441-55. doi: 10.1517/17425255.2011.557066. Epub 2011 Feb 19.
Parkinson's disease (PD) is a progressive neurodegenerative disorder. To date, most of the currently available therapies in PD target the dopaminergic system and none of these therapeutic approaches have been proven to modify the course of the disease. To various extents, these drugs can also cause motor and non-motor complications. A novel target, the adenosine A(2A) receptor (AA2AR), was recently identified, blockade of which may alleviate Parkinsonian symptoms, reduce motor fluctuations and potentially afford neuroprotection.
This review is based on a PubMed search covering the relationship of the adenosine receptors and PD. The role of the AA2AR is reviewed and the results of preclinical investigations of antagonists are assessed. A synopsis of current drug development is provided, with a special focus on the pharmacokinetics and relevant clinical trials.
The localization of the AA2AR in the central nervous system, the ultra structural localization and the molecular mechanism of its action reveal the potential importance of the AA2AR in movement disorders. The theoretical background and experimental data indicate that AA2AR antagonists may have a potential therapeutic effect in Parkinson's disease. More importantly, the putative neuroprotective effect needs further investigation.
帕金森病（PD）是一种进行性神经退行性疾病。迄今为止，PD 中大多数现有的治疗方法都针对多巴胺能系统，而这些治疗方法都没有被证明能够改变疾病的进程。这些药物在不同程度上也会引起运动和非运动并发症。最近发现了一个新的靶点，即腺苷 A（2A）受体（AA2AR），其阻断可能减轻帕金森病症状、减少运动波动并可能提供神经保护作用。
这篇综述基于对涵盖腺苷受体与 PD 关系的 PubMed 搜索。综述了 AA2AR 的作用，并评估了其拮抗剂的临床前研究结果。提供了当前药物开发的概述，特别关注药代动力学和相关临床试验。
AA2AR 在中枢神经系统中的定位、超微结构定位及其作用的分子机制揭示了 AA2AR 在运动障碍中的潜在重要性。理论背景和实验数据表明，AA2AR 拮抗剂可能对帕金森病具有潜在的治疗作用。更重要的是，假定的神经保护作用需要进一步研究。
