Prediction of the human brain distribution for the central nervous system drugs using a novel human immortalized brain capillary endothelial cells

基于人血脑屏障（BBB）转运功能预测药物的脑分布，不仅对开发新的中枢神经系统（CNS）作用药物，而且对中枢神经系统疾病的药物治疗具有重要意义。本研究的目的是利用人脑毛细血管内皮细胞系hCMEC/D3 （D3）的体外模型，阐明阳离子转运蛋白的功能表达。本研究还探讨了D3细胞体外摄取研究的结果是否可以外推到人血脑屏障。本研究发现，阳离子转运蛋白（OCTN2、OCTN1、PMAT和H^+/有机阳离子反转运蛋白）在D3细胞中有功能性表达。此外，可以建立一种利用D3细胞从体外数据推断cnns作用药物在人脑内分布的方法。

Prediction of the brain distribution of drugs, based on the transport function of the human blood-brain barrier (BBB), is important for not only development of new central nervous system (CNS)-acting drugs, but also pharmacotherapy for CNS diseases. The purpose of this study is to clarify the functional expression of cation transporters using human brain capillary endothelial cell line hCMEC/D3 (D3), an in vitro model. The study was also investigated whether or not the results of in vitro uptake study using D3 cells can be extrapolated to human BBB. In this study, it was found that cationic transporters (OCTN2, OCTN1, PMAT and H^+/organic cation antiporter) are functionally expr essed in D3 cells. Further, a method can be established for extrapolating brain distribution of theCNS-acting drugs in human from the in vitro data using D3 cells.