Department of Neurology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Weifang People's Hospital, Weifang, Shandong, China.
Curr Neuropharmacol. 2023;21(8):1806-1826. doi: 10.2174/1570159X20666220222150811.
Nondopaminergic neurotransmitters such as adenosine, norepinephrine, serotonin, glutamate, and acetylcholine are all involved in Parkinson's disease (PD) and promote its symptoms. Therefore, nondopaminergic receptors are key targets for developing novel preparations for the management of motor and non-motor symptoms in PD, without the potential adverse events of dopamine replacement therapy. We reviewed English-written articles and ongoing clinical trials of nondopaminergic treatments for PD patients till 2014 to summarize the recent findings on nondopaminergic preparations for the treatment of PD patients. The most promising research area of nondopaminergic targets is to reduce motor complications caused by traditional dopamine replacement therapy, including motor fluctuations and levodopa-induced dyskinesia. Istradefylline, Safinamide, and Zonisamide were licensed for the management of motor fluctuations in PD patients, while novel serotonergic and glutamatergic agents to improve motor fluctuations are still under research. Sustained- release agents of Amantadine were approved for treating levodopa induced dyskinesia (LID), and serotonin 5HT1B receptor agonist also showed clinical benefits to LID. Nondopaminergic targets were also being explored for the treatment of non-motor symptoms of PD. Pimavanserin was approved globally for the management of hallucinations and delusions related to PD psychosis. Istradefylline revealed beneficial effect on daytime sleepiness, apathy, depression, and lower urinary tract symptoms in PD subjects. Droxidopa may benefit orthostatic hypotension in PD patients. Safinamide and Zonisamide also showed clinical efficacy on certain non-motor symptoms of PD patients. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs may lead to new approaches with positive clinical implications.
非多巴胺能神经递质如腺苷、去甲肾上腺素、血清素、谷氨酸和乙酰胆碱都与帕金森病（PD）有关，并促进其症状。因此，非多巴胺能受体是开发新型制剂以管理 PD 运动和非运动症状的关键靶点，而没有多巴胺替代疗法的潜在不良反应。我们回顾了截至 2014 年有关 PD 患者非多巴胺能治疗的英文文献和正在进行的临床试验，以总结非多巴胺能制剂治疗 PD 患者的最新发现。非多巴胺能靶点最有前途的研究领域是减少传统多巴胺替代疗法引起的运动并发症，包括运动波动和左旋多巴诱导的运动障碍。依曲替酯、沙芬酰胺和唑尼沙胺被许可用于管理 PD 患者的运动波动，而改善运动波动的新型血清素和谷氨酸能药物仍在研究中。盐酸金刚烷胺的缓释剂被批准用于治疗左旋多巴诱导的运动障碍（LID），而 5-HT1B 受体激动剂也显示出对 LID 的临床益处。非多巴胺能靶点也在探索用于治疗 PD 的非运动症状。哌马色林在全球范围内被批准用于治疗与 PD 精神病相关的幻觉和妄想。依曲替酯对 PD 患者的日间嗜睡、淡漠、抑郁和下尿路症状有有益的影响。屈昔多巴可能对 PD 患者的直立性低血压有益。沙芬酰胺和唑尼沙胺也对某些 PD 患者的非运动症状显示出临床疗效。非多巴胺能药物预计不会替代多巴胺能策略，但这些药物的进一步发展可能会带来具有积极临床意义的新方法。
