IRCCS National Neurological Institute C. Mondino, Center for Research in Neurodegenerative Diseases , Via Mondino 2, 27100 Pavia , Italy +39 0382 380416 ; +39 0382 380448 ;
Expert Opin Investig Drugs. 2014 Mar;23(3):387-410. doi: 10.1517/13543784.2014.869209. Epub 2013 Dec 9.
Prolonged administration of l-3,4-dihydroxyphenylalanine (l-DOPA) for Parkinson's disease (PD) is hampered by motor complications related to the progressive incapacity of residual nigrostriatal neurons to properly utilize the drug. Direct stimulation of dopaminergic (DAergic) receptors with specific compounds (DA agonists) has, therefore, become an additional therapeutic tool for PD.
DA agonists have considerable anti-parkinsonian symptomatic efficacy, although they are less potent than l-DOPA. This review summarizes pre-clinical and clinical data on DA agonists and their role in treating PD. Specific focus was put on second-generation, first-line non-ergolinic DA agonists and their motor, non-motor and putative neuroprotective effects. The anti-parkinsonian potential of recently developed DA agonists that reached Phase II and III clinical trials was also addressed.
DA agonists can be useful along the whole natural course of PD, as monotherapy in the initial phase or combined with l-DOPA in advanced PD. Extended-release formulations have been developed for second-generation DA agonists, which are better appreciated by patients. Neuroprotective properties have been proposed for DA agonists, based on pre-clinical studies, but never convincingly demonstrated in patients. New DA agonists, with better symptomatic efficacy and devoid of the side effects that characterize current compounds, are needed.
左旋多巴（l-DOPA）治疗帕金森病（PD）的时间延长，会受到与残余黑质纹状体神经元逐渐丧失正确利用药物相关的运动并发症的阻碍。因此，用特定化合物（多巴胺激动剂）直接刺激多巴胺能（DAergic）受体已成为 PD 的另一种治疗工具。
DA 激动剂具有相当大的抗帕金森病症状功效，尽管它们的功效不如 l-DOPA 强。这篇综述总结了关于 DA 激动剂及其在治疗 PD 中的作用的临床前和临床数据。特别关注第二代、一线非麦角类 DA 激动剂及其运动、非运动和潜在的神经保护作用。还讨论了最近开发的、已进入 II 期和 III 期临床试验的 DA 激动剂的抗帕金森病潜力。
DA 激动剂可在 PD 的整个自然病程中有用，可作为初始阶段的单一疗法或与 l-DOPA 联合用于晚期 PD。已为第二代 DA 激动剂开发了缓释制剂，这些制剂更受患者欢迎。基于临床前研究，提出了 DA 激动剂具有神经保护作用，但从未在患者中得到令人信服的证明。需要新的 DA 激动剂，具有更好的症状功效，且没有当前化合物的副作用。
