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1、ReviewNewadvancesinNMDAreceptorpharmacologyKevinK.OgdenandStephenF.TraynelisDepartmentofPharmacology,EmoryUniversitySchoolofMedicine,5025RollinsResearchCenter,1510CliftonRoad,Atlanta,GA30322,USAN-Methyl-D-aspartate(NMDA)receptorsaretetramericpromisethatsubunit-selectiveagonists,antagonistsand
2、ionchannelscontainingtwooffourpossibleGluN2sub-modulatorscouldbefoundthatwouldallowNMDArecep-units.Thesereceptorshavebeenimplicatedfordecadestorfunctiontoberegulatedinaregion-specificmanner.inneurologicaldiseasessuchasstroke,traumaticbrainThishopeinitiallyseemedtobewellfounded,asextensiveinjur
3、y,dementiaandschizophrenia.TheGluN2subunitspharmacologywasdevelopedaroundtheGluN2Bsubunit,substantiallycontributetofunctionaldiversityofNMDAtriggeredbythediscoverythattheantihypertensiveagentreceptorsandaredistinctlyexpressedduringdevelop-ifenprodilwasasubunit-selectiveantagonistforNMDAmentan
4、damongbrainregions.Thus,subunit-selectivereceptorscontainingtheGluN2Bsubunit[2].However,antagonistsandmodulatorsthatdifferentiallytargettheshortlyafterthisperiodofsustainedprogress,discoveryofGluN2subunitmightprovideanopportunitytopharma-newligandsandpharmacologicaltoolsstalled.Forovertencolo
5、gicallymodifythefunctionofselectgroupsofneu-yearsthereseemedtobelittleadvanceinthedevelopmentronsfortherapeuticgain.Aflurryofclinical,functionalofsubunit-selectiveantagonistsandmodulatorsforNMDAandchemicalstudieshavetogetherreinvigoratedeffortsreceptorscomprisingsubunitsotherthanGluN2Btoidenti
6、fysubunit-selectivemodulatorsofNMDArecep-(Figure1).Moreover,thispauseindiscoverycoincidedtorfunction,resultinginahandfulofnewcompoundswiththerealizationthattheclinicalutilityofNMDAthatappeartoactatnovelsites.Here,wereviewthereceptorantagonistsinneurologicaldiseasessuchaspropertiesofnewemergin
7、gclassesofsubunit-selectivestroke,traumaticbraininjuryanddementiawasmoreNMDAreceptormodulators,whichwepredictwillmarkcomplexthaninitiallyappreciated,asamultitudeofclini-thebeginningofaproductiveperiodofprogressforcaltrialsinvolvingawiderangeo