Laboratory of Cellular and Molecular Neurobiology, IRCCS Mondino Foundation , Pavia, Italy.
Department of Brain and Behavioral Sciences, University of Pavia , Pavia, Italy.
Expert Opin Pharmacother. 2020 Dec;21(18):2279-2291. doi: 10.1080/14656566.2020.1805432. Epub 2020 Aug 17.
Long-term treatment of Parkinson's disease (PD) with levodopa is hampered by motor complications related to the inability of residual nigrostriatal neurons to convert levodopa to dopamine (DA) and use it appropriately. This generated a tendency to postpone levodopa, favoring the initial use of DA agonists, which directly stimulate striatal dopaminergic receptors. Use of DA agonists, however, is associated with multiple side effects and their efficacy is limited by suboptimal bioavailability.
This paper reviewed the latest preclinical and clinical findings on the efficacy and adverse effects of non-ergot DA agonists, discussing the present and future of this class of compounds in PD therapy.
The latest findings confirm the effectiveness of DA agonists as initial treatment or adjunctive therapy to levodopa in advanced PD, but a more conservative approach to their use is emerging, due to the complexity and repercussions of their side effects. As various factors may increase the individual risk to side effects, assessing such risk and calibrating the use of DA agonists accordingly may become extremely important in the clinical management of PD, as well as the availability of new DA agonists with better profiles of safety and efficacy.
左旋多巴治疗帕金森病（PD）的长期治疗受到与残余黑质纹状体神经元将左旋多巴转化为多巴胺（DA）的能力下降相关的运动并发症的阻碍，无法正确使用。这导致了推迟使用左旋多巴的趋势，倾向于最初使用直接刺激纹状多巴胺能受体的 DA 激动剂。然而，DA 激动剂的使用与多种副作用相关，其疗效受到生物利用度不佳的限制。
本文综述了关于非麦角类 DA 激动剂在疗效和不良反应方面的最新临床前和临床研究结果，讨论了这类化合物在 PD 治疗中的现状和未来。
最新发现证实了 DA 激动剂作为晚期 PD 患者初始治疗或与左旋多巴联合治疗的有效性，但由于其副作用的复杂性和影响，对其使用的态度更加保守。由于各种因素可能会增加个体发生副作用的风险，因此评估这种风险并相应调整 DA 激动剂的使用可能在 PD 的临床管理中以及新的 DA 激动剂的可用性变得非常重要，这些新的 DA 激动剂具有更好的安全性和疗效特征。
