Wang Wen-Wen, Zhang Man-Man, Zhang Xing-Ru, Zhang Zeng-Rui, Chen Jie, Feng Liang, Xie Cheng-Long
The Center of Traditional Chinese Medicine, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Neurol. 2017 Dec 22;8:702. doi: 10.3389/fneur.2017.00702. eCollection 2017.
Long-term use of levodopa (l-dopa) is inevitably complicated with highly disabling fluctuations and drug-induced dyskinesias, which pose major challenges to the existing drug therapy of Parkinson's disease.
In this study, we conducted a systematic review and meta-analysis to assess the efficacy of A2A receptor antagonists on reducing l-dopa-induced dyskinesias (LID).
Nine studies with a total of 152 animals were included in this meta-analysis. Total abnormal involuntary movements (AIM) score, locomotor activity, and motor disability were reported as outcome measures in 5, 5, and 3 studies, respectively. Combined standardized mean difference (SMD) estimates were calculated using a random-effects model. We pooled the whole data and found that, when compared to l-dopa alone, A2A receptor antagonists plus l-dopa treatment showed no effect on locomotor activity (SMD -0.00, 95% confidence interval (CI): -2.52 to 2.52, = 1.0), superiority in improvement of motor disability (SMD -5.06, 95% CI: -9.25 to -0.87, = 0.02) and more effective in control of AIM (SMD -1.82, 95% CI: -3.38 to -0.25, = 0.02).
To sum up, these results demonstrated that A2A receptor antagonists appear to have efficacy in animal models of LID. However, large randomized clinical trials testing the effects of A2A receptor antagonists in LID patients are always warranted.
长期使用左旋多巴（L-多巴）不可避免地会出现严重致残的运动波动和药物性异动症，这对帕金森病现有的药物治疗构成了重大挑战。
在本研究中，我们进行了一项系统评价和荟萃分析，以评估A2A受体拮抗剂在减少左旋多巴诱导的异动症（LID）方面的疗效。
本荟萃分析纳入了9项研究，共152只动物。分别有5项、5项和3项研究将总异常不自主运动（AIM）评分、运动活性和运动功能障碍作为结局指标。使用随机效应模型计算合并标准化均数差（SMD）估计值。我们汇总了全部数据，发现与单独使用左旋多巴相比，A2A受体拮抗剂联合左旋多巴治疗对运动活性无影响（SMD -0.00，95%置信区间（CI）：-2.52至2.52，P = 1.0），在改善运动功能障碍方面具有优势（SMD -5.06，95%CI：-9.25至-0.87，P = 0.02），并且在控制AIM方面更有效（SMD -1.82，95%CI：-3.38至-0.25，P = 0.02）。
综上所述，这些结果表明A2A受体拮抗剂在LID动物模型中似乎具有疗效。然而，始终需要进行大型随机临床试验来测试A2A受体拮抗剂对LID患者的影响。
