Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems.
Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems.
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DOI：
10.1007/bf03206642
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Tsuji, Akira
中科院分区：
文献类型：
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作者：
Tsuji, Akira
由于血脑屏障（BBB）的生理特性，化合物在血液和脑之间的运输被广泛认为是通过被动扩散的方式发生的，这取决于化合物的亲脂性。然而，在许多情况下，亲脂性和明显血脑屏障渗透特性之间存在差异，这些差异可归因于药物通过血脑屏障转运的多种机制的存在。内流转运蛋白（从血液到脑）和外流转运蛋白（从脑到血液）的分子鉴定和功能分析进展迅速。因此，血脑屏障现在被认为是一个动态界面，控制各种物质的流入和流出，包括内源性营养物质和外源性化合物（如药物），以维持一个有利的中枢神经系统环境。本文综述了转运系统在外源药物（包括有机阴离子/阳离子和中性药物）通过血脑屏障进入大脑中的作用，以及通过阻断外排转运蛋白功能增加药物进入大脑的策略，或通过调节血脑屏障转运过程减少中枢神经系统副作用的策略。
Because of the physiological nature of the blood-brain barrier (BBB), transport of chemical compounds between blood and brain has been widely believed to occur by means of passive diffusion, depending upon the lipophilicity of the compounds. However, discrepancies exist between the lipophilicity and apparent BBB permeation properties in many cases, and these discrepancies can be ascribed to the existence of multiple mechanisms of drug transport through the BBB. Molecular identification and functional analysis of influx transport proteins (from blood to brain) and efflux transport proteins (from brain to blood) have progressed rapidly. Therefore, the BBB is now considered to be a dynamic interface that controls the influx and efflux of a wide variety of substances, including endogenous nutrients and exogenous compounds such as drugs, to maintain a favorable environment for the CNS. This review focuses on the role of transport systems in the uptake of xenobiotics, including organic anionic/cationic and neutral drugs, across the BBB into the brain, as well as on strategies to increase drug delivery into the brain by blocking efflux transport protein function, or to reduce CNS side effects by modulating BBB transport processes.