Axe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada.
Axe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada; Faculty of Pharmacy, Laval University, Quebec, QC, Canada.
Front Neuroendocrinol. 2024 Oct;75:101156. doi: 10.1016/j.yfrne.2024.101156. Epub 2024 Sep 29.
Parkinson's disease (PD) is characterized by motor symptoms due to loss of brain dopamine and non-motor symptoms, including gastrointestinal disorders. Although there is no cure for PD, symptomatic treatments are available. L-Dopa is the gold standard PD therapy, but most patients develop dyskinesias (LID), which are challenging to manage. Amantadine is recognized as the most effective drug for LID, but its adverse effects limit the use in patients. Here we review how 5α-reductase inhibitors (5ARIs), drugs used to treat benign prostatic hyperplasia and alopecia, exhibit beneficial effects in PD animal models. 5ARIs show neuroprotective properties in brain and gut dopaminergic systems, and reduce dyskinesias in rodent model of PD. Additionally, the 5ARI finasteride dampened dopaminergic-induced drug gambling in PD patients. Neuroprotection and antidyskinetic activities of 5ARIs in animal models of PD suggest their potential repurposing in men with PD to address gut dysfunction, protect brain DA and inhibit dyskinesias.
帕金森病（PD）的特征是由于大脑多巴胺的丧失导致运动症状和非运动症状，包括胃肠道紊乱。虽然 PD 无法治愈，但有对症治疗方法。左旋多巴是 PD 的金标准治疗药物，但大多数患者会出现运动障碍（LID），这很难进行管理。金刚烷胺被认为是治疗 LID 最有效的药物，但它的不良反应限制了其在患者中的使用。在这里，我们回顾了 5α-还原酶抑制剂（5ARIs），即用于治疗良性前列腺增生和脱发的药物，如何在 PD 动物模型中表现出有益的效果。5ARIs 在大脑和肠道多巴胺能系统中表现出神经保护特性，并减少 PD 啮齿动物模型中的运动障碍。此外，5ARI 非那雄胺可抑制 PD 患者多巴胺诱导的药物成瘾。5ARIs 在 PD 动物模型中的神经保护和抗运动障碍作用表明它们有可能被重新用于治疗 PD 男性的肠道功能障碍，保护大脑中的 DA 并抑制运动障碍。
