Bawa Priya, Pradeep Priyamvada, Kumar Pradeep, Choonara Yahya E, Modi Girish, Pillay Viness
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
Drug Discov Today. 2016 Dec;21(12):1886-1914. doi: 10.1016/j.drudis.2016.08.001. Epub 2016 Aug 6.
Historically, neuropsychiatric and neurodegenerative disease treatments focused on the 'magic bullet' concept; however multi-targeted strategies are increasingly attractive gauging from the escalating research in this area. Because these diseases are typically co-morbid, multi-targeted drugs capable of interacting with multiple targets will expand treatment to the co-morbid disease condition. Despite their theoretical efficacy, there are significant impediments to clinical success (e.g., difficulty titrating individual aspects of the drug and inconclusive pathophysiological mechanisms). The new and revised diagnostic frameworks along with studies detailing the endophenotypic characteristics of the diseases promise to provide the foundation for the circumvention of these impediments. This review serves to evaluate the various marketed and nonmarketed multi-targeted drugs with particular emphasis on their design strategy.
从历史上看，神经精神疾病和神经退行性疾病的治疗侧重于“神奇子弹”概念；然而，从该领域不断增加的研究来看，多靶点策略越来越具有吸引力。由于这些疾病通常是共病的，能够与多个靶点相互作用的多靶点药物将把治疗扩展到共病疾病状态。尽管它们在理论上有效，但临床成功仍存在重大障碍（例如，难以调整药物的各个方面以及病理生理机制尚无定论）。新的和修订的诊断框架以及详细描述疾病内表型特征的研究有望为克服这些障碍提供基础。本综述旨在评估各种已上市和未上市的多靶点药物，特别强调其设计策略。
