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Pharmacological profile of PMS777, a new AChE inhibitor with PAF antagonistic activity

By Antonio Reed,2014-02-18 17:11
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Pharmacological profile of PMS777, a new AChE inhibitor with PAF antagonistic activity

    Pharmacological profile of PMS777, a new

    AChE inhibitor with PAF antagonistic

    activity

    PharmacologicalprofileofPMS777,anewAChEinhibitorwithPAF

    antagonisticactivity.

    LiJ,HuangH,MiezanEzoulinJM,GaoXL,MassicotF,DongCZ,HeylnansF,ChenHZ Depal'tnaentofPharmacology,CollegeofBasicMedicalSciences,ShanghaiJiaotongUi1iversity,Shanghai,PRChina

    Thekeypathophysiological111echallis111sinAlzheilner'sdiseaseinvolvetheselectivelossofcholinergicneuronsand

    proilaflalnmatorymediator

    rclatedchronicinflanmaatoryresponsesinthebrain,thereforeinterventiolasofthese processesarecrucialtothetreatlnentofthisdisease.Inthepresentstudy,thepharmacologicalprofileofPMS777,

    anewacetylcholinesterase(AChE)inhibitorwithplatelet

    activatingfactor(PAF)antagonisticactivity,hasbeen

    evaluatedil!vitroandil!vivo.PMS777(1100muM)dosedependentlyinhibitedPAF

    inducedrabbitplateletaggre

    gationbycompetingwith[3H]PAFforitsreceptoronplatelets,andprotectedahu1TlanneuroblastomacelllineSH

    SY5YagainstPAF

    inducedneurotoxicity.Moreover,itmarkedlyinhibitedbrainAChEactivityinmiceandshowed

    amodestselectivityforAChE(AChE:IC50=2.48+/

    0.12nmM;butyrylcholinesterase:IC50=4.47+/0.15muM).Ex

    Vi,PMS777(5,10,20or40mg/kgi.p.)reducedbrainACl-ff';activityilladose

dependentreal-tiler.Invivostudies

    revealedthatPMS777(0.25,0.5,1,2.5or5mg/kgi.p.)couldreversescopolalnine

    inducedmemoryretrieval

    dcficitsil!mice,anddisplayedatypicalbellshapeddose

    responserelationship.Takentogether,theseresultsdem-

    onstratethatPMS777possessesdualactivitiesforPAFreceptorantagoniS1T1andAChEinhibition.suggestingthat

    thiscompoundmaybeaprolnisingleadcompouladforfurtherilwestigationrelatedtothetreatlnentforAlzlaeimer's

    djsease

    /ntJNeuropsychopharmaco1.2006Jan23:19[Epubaheadofprint](impactfactor:3.981)

    PreparationandinvitroandinvivoreleasestudiesofHuperzineA

    loadedmicrospheresforthetreatmentofAlzheimer'sdisease.

    LiuWH,Song,LiuK,ClmOF,LiYX

    SchoolofPharmacy,YantaiUniversity,264005Yantai,ShandongProvince,PRChina ThepurposeofthisstudywastopreparemicrospherescontainingHuperzineA,whichisusedforpatientssuffering

    frornAlzheimer'sdiseasebecauseofitspotentanticlaolineestaseactivity,andtoclarifyinvitroandinvivorelease

    characteristicsofthem.Thepreparationandinvitroandil!vivoreleasestudiesofI-IuperzineAloadedmicrospheres

    weredescribed.Byspraydryingmetlaod,HuperzineAwasencapsulatedsuccessflfllyinthemicrosphereswhich

    weresphericalwithanon

    porousandsmoothsurface.InvitrostudiesshowedthatthereleaseofHuperzineAfrom microsphereswasdependedonthepropertiesofpolymersandthereleaselnedium.Counterionicinteractionbe

    tweentheprimaryamilaegroupofHuperzineAandthecarboxylicterminalgroupofPLGpolymersimprovesthe

    encapsulationofHuperzine

,reducingtheinitialburstandextendingthesustainedrelease.Highmolecularweight

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