Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Department of Medical Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Curr Pharm Des. 2020;26(13):1466-1485. doi: 10.2174/1381612826666200224112534.
An important goal of biomedical research is to translate basic research findings into practical clinical implementation. Despite the advances in the technology used in drug discovery, the development of drugs for central nervous system diseases remains challenging. The failure rate for new drugs targeting important central nervous system diseases is high compared to most other areas of drug discovery. The main reason for the failure is the poor penetration efficacy across the blood-brain barrier. The blood-brain barrier represents the bottleneck in central nervous system drug development and is the most important factor limiting the future growth of neurotherapeutics. Meanwhile, drug repositioning has been becoming increasingly popular and it seems a promising field in central nervous system drug development. In vitro blood-brain barrier models with high predictability are expected for drug development and drug repositioning. In this review, the recent progress of in vitro BBB models and the drug repositioning for central nervous system diseases will be discussed.
生物医学研究的一个重要目标是将基础研究成果转化为实际的临床应用。尽管在药物发现中使用的技术取得了进步,但中枢神经系统疾病药物的开发仍然具有挑战性。与大多数其他药物发现领域相比,针对重要中枢神经系统疾病的新药开发失败率很高。失败的主要原因是穿过血脑屏障的渗透效果不佳。血脑屏障是中枢神经系统药物开发的瓶颈,也是限制神经治疗学未来发展的最重要因素。同时,药物重定位越来越受到关注,在中枢神经系统药物开发中似乎是一个很有前景的领域。具有高预测性的体外血脑屏障模型有望应用于药物开发和药物重定位。本文将讨论体外 BBB 模型的最新进展和中枢神经系统疾病的药物重定位。