Stereoselective study of fluoxetine and norfluoxetine across the blood–brain barrier mediated by organic cation transporter 1/3 in rats using an enantioselective UPLC‐MS/MS method

Author:

An Hai1,Fang Jinjun1,Wang Min1,Lin Haiyang1,Sun Yingying1,Hu Bingying1,He Zhisheng1,Ge Zhen1,Wei Yang1ORCID

Affiliation:

1. Zhejiang Key Laboratory of Neuropsychiatric Drug Research, School of Pharmacy Hangzhou Medical College Hangzhou Zhejiang China

Abstract

AbstractFluoxetine (FLT) is a widely used antidepressant in clinical practice, which can be metabolized into active norfluoxetine (NFLT) in vivo. The stereoselectivity of FLT and NFLT enantiomers across the blood–brain barrier (BBB) is still to be clarified. In this study, accurate and reliable UPLC‐MS/MS enantioselective analysis was established in rat plasma and brain. The characteristics of FLT and NFLT enantiomers across the BBB were studied by chemical knockout of rat transporters. We found that the dominant enantiomers of FLT and NFLT were S‐FLT and R‐NFLT, respectively, both in plasma and in brain. The FLT and NFLT enantiomers showed significant stereoselectivity across the BBB, and S‐FLT and S‐NFLT were the dominant configurations across the BBB. Chemical knockout of organic cation transporter 1 (OCT1) and OCT3 can affect the ratio of plasma FLT and NFLT enantiomers into the brain, suggesting that OCT1/3 is stereoselective for FLT and NFLT transport across the BBB.

Publisher

Wiley

Subject

Organic Chemistry,Spectroscopy,Drug Discovery,Pharmacology,Catalysis,Analytical Chemistry

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3