有机阳离子转运体在脑内分布的药理学意义  

Pharmacological Significance of the Expression of Organic Cation Transporters in the Brain

作　　者：刘晓楠 刘晓东[1] 刘李[1] LIU Xiaonan;LIU Xiaodong;LIU Li(Center of Drug Metabolism and Pharmacokinetics,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院药物代谢研究中心,江苏南京210009

出　　处：《药学进展》2021年第7期524-531,共8页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金面上项目(No.81872930,No.82073922,No.81673505);江苏省“333”工程(No.BRA2020287)。

摘　　要：有机阳离子转运体(OCT)是一类多功能双向转运体,参与有机阳离子药物、毒物以及内源性物质的转运。OCT包括OCT1、OCT2和OCT3这3种转运蛋白,其在肝、肠和肾等外周组织表达量较高,在大脑中表达量较低,但发挥着重要作用。有证据表明,OCT可能在多巴胺转运体、去甲肾上腺素转运体和5-羟色胺转运体等单胺类递质高亲和转运体被阻断后发挥代偿作用;OCT在血脑屏障中表达的改变可能影响某些外源性药物和毒性物质的脑内浓度;OCT介导的药物相互作用可能增加某些药物中枢神经系统毒副作用的风险。综述了OCT在脑内的分布,以及其在脑内内源性物质稳态调控中的作用和在药理学研究中的意义,旨在为进一步研究OCT在脑内药物转运和脑内疾病中的作用提供参考。Organic cation transporters(OCTs)are multispecific bidirectional transporters that participate in the transport of organic cation drugs,toxins and endogenous substances.OCTs include OCT1,OCT2 and OCT3,with high expression in peripheral tissues such as liver,intestine and kidney,and low expression in the brain,playing an important role.Evidence indicates that OCTs may play a compensatory role when monamine transmitters with high affinity such as dopamine transporter,norepinephrine transporter and serotonin transporter are blocked.The change of OCTs at blood-brain barrier may affect concentrations of some exogenous drugs and toxic substances in the brain.OCT-mediated drug interactions may increase the risk of side effects with the central nervous system.The distribution of OCTs in the brain,the role of OCTs in homeostasis maintenance in the brain and the significance in pharmacological research are reviewed,aiming to provide reference for the further study of OCTs in drug transport and intracerebral diseases.

关 键 词：有机阳离子转运体 单胺类递质 血脑屏障 药物相互作用 

分 类 号：R969.1[医药卫生—药理学]