Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel A Potential Mechanism for Their Neuroprotective Effects 英文参考文献.docVIP

下载本文档

0
0
约3.35万字
约 8页
2017-05-11 发布于上海
举报
版权申诉

Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel A Potential Mechanism for Their Neuroprotective Effects 英文参考文献.doc

1、本文档共8页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

ArylbenzazepinesArePotentModulatorsfortheDelayedRectifierKChannelAPotentialMechanismforTheirNeuroprotectiveEffects英文参考文献

ArylbenzazepinesArePotentModulatorsfortheDelayed RectifierK Channel:APotentialMechanismforTheir NeuroprotectiveEffects + Xue-QinChen1,JingZhang2,JohnL.Neumeyer3,Guo-ZhangJin1,Guo-YuanHu1,AoZhang2*, XuechuZhen1* 1StateKeylaboratoryofDrugResearch,DepartmentofPharmacologyII,ShanghaiInstituteofMateriaMedica,ChineseAcademyofSciences,Shanghai,China,2Synthetic Organic Medicinal Chemistry Laboratory (SOMCL),Shanghai Institute ofMateria Medica, Chinese Academy ofSciences, Shanghai,China, 3Alcoholand DrugAbuse ResearchCenter,McLeanHospital,HarvardMedicalSchool,Belmont,Massachusetts,UnitedStatesofAmerica Abstract (6)SKF83959,likemanyotherarylbenzazepines,elicitspowerfulneuroprotectioninvitroandinvivo.Theneuroprotective action of the compound was found to partially depend on its D1-like dopamine receptor agonistic activity. The precise mechanismforthe(6)SKF83959-mediatedneuroprotectionremainselusive.Wereportherethat(6)SKF83959isapotent + + blockerfordelayedrectifierK channel.(6)SKF83959inhibitedthedelayedrectifierK current(I )dose-dependentlyinrat K hippocampalneurons.TheIC valueforinhibitionofI was41.962.3mM(Hillcoefficient=1.8160.13,n=6),whereasthat 50 K forinhibitionofIA was307.9638.5mM(Hillcoefficient=1.3760.08,n=6).Thus,(6)SKF83959 is7.3-foldmorepotentin suppressingIKthanIA.Moreover,theinhibitionofIKby(6)SKF83959wasvoltage-dependentandnotrelatedtodopamine receptors.Therapidlyonsetofinhibitionandrecoverysuggeststhattheinhibitionresultedfromadirectinteractionof(6) + SKF83959 with the K channel. The intracellular application of (6) SKF83959 had no effects of on IK, indicating that the compoundmostlikelyactsattheoutermouthoftheporeofK channel.Wealsotestedtheenantiomersof(6 )SKF83959, + R-(+)SKF83959(MCL-201),andS-(2)SKF83959(MCL-202),aswellasSKF38393;allthesecompoundsinhibitedIK .However, (6)SKF83959,ateither0.1or1mM,exhibitedthestrongestinhibitiononthecurrentsamongalltesteddrug.Thepresent findingsnotonlyrevealedanewpotentblockerofIK,butalsoprovidedan