Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Department of Pharmacology, Government Medical College and Hospital Chandigarh, India.
Eur J Pharmacol. 2018 Jul 5;830:115-127. doi: 10.1016/j.ejphar.2018.04.023. Epub 2018 Apr 22.
Parkinson's disease (PD) is a chronic progressive neurological disorder characterized by accumulation of Lewy bodies and profound loss of substantia nigra dopaminergic neurons. PD symptomatology is now recognized to include both cardinal motor as well as clinically significant non-motor symptoms. Despite intensive research, the current understanding of molecular mechanisms underlying neurodegeneration in PD is limited and has hampered the development of novel symptomatic and disease modifying therapies. The currently available treatment options are only partially or transiently effective and fail to restore the lost dopaminergic neurons or retard disease progression. Given the escalating drug development costs, lengthening timelines and declining R&D efficiency, industry and academia are increasingly focusing on ways to repurpose existing molecules as an accelerated route for drug discovery. The field of PD therapeutics is witnessing vigorous repurposing activity supported by big data analytics, computational models, and high-throughput drug screening systems. Here we review the mechanisms, efficacy, and safety of several emerging drugs currently aspiring to be repositioned for PD pharmacotherapy.
帕金森病（PD）是一种慢性进行性神经退行性疾病，其特征是Lewy 体的积累和黑质多巴胺能神经元的明显丧失。现在已经认识到 PD 的症状包括主要的运动症状以及临床上重要的非运动症状。尽管进行了深入的研究，但目前对 PD 神经退行性变分子机制的理解仍然有限，这阻碍了新型对症和疾病修饰治疗方法的发展。目前可用的治疗选择仅部分或短暂有效，无法恢复丢失的多巴胺能神经元或延缓疾病进展。鉴于不断上升的药物开发成本、延长的时间线和不断下降的研发效率，工业界和学术界越来越关注将现有分子重新用于药物发现的途径。PD 治疗学领域正在见证由大数据分析、计算模型和高通量药物筛选系统支持的积极重新定位活动。在这里，我们回顾了几种新兴药物的机制、疗效和安全性，这些药物目前有望被重新定位用于 PD 药物治疗。
