第3代抗精神病药阿立哌唑研究进展

3,(,201108)R971+14A1672-2124(2005)02-0121-03,,1(FGA)2(SGA),,3(TGA)[1,2],,,,-,;-,,,,;,FGASGA-;D2,,-EPS()TD();,SGAEPS(),5-HT2A[3,4],D25-HT1A(),5-HT2A,-D2FGASGA[57]1988,,FDA200110,200211152003(EMEA)2004[2,8]1D25-HT1A,5-HT2A;D3;:D45-HT2C5-HT71H1,5-(SERT);M(1),D2,[5,812]111510152030mg1Ki(nM)Ki(nM)D12655-HT1A1.7D20.345-HT2A3.4D30.85-HT2C15D4445-HT6214D5955-HT739SERT398157M(IC50,nM)(1000)H1613SERT=1015mgPd,,3h5h,87%,99%,D275h95h2CYP2D63A440%;14C,25%50%18%,1%[2,5,9]112,DA(D2,cAMP,DA,DAD2DA,,-,,DA()D2DA,DA,D2,5-HT2A,EPS,5-HT1A,,200552121©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.DA2,[8,11,12]2[1,3,1214],,FDA,44(15mg30mgPd)(10mgPd)4(n=414)282132,,4:PANSSPANSSPBPRS()CQI15mgPdPANSS,2,15mg30mgPd,4,40420mg30mgPd6mg,3;CGI12,20mg30mgPd,21,307,21030mgPd10mgPd4,3;30mgPd,CGIBPRSPANSS,1,530mgPd,10mg15mg20mgPd3,6(pooledanalysis)898,10mgPd,1212631015mgPd,,,(34%57%)6,PANSS,152129430mgPd(n=861)10mgPd(n=433)82652,PANSS,2652,,(adherence)Kujawa,,1103[4,5,13,15],,,,5,;EPS,;,,14,,,:9.4%,8.0%,7.3%52,,,,EPS,(Simpson-AngusScale,SAS)(AbnormalInvoluntaryMovementScale,AIMS)(BarnesAkathisiaRatingScale,BAS)SAS,AIMS,BASSASBASEPS,,,,10%5%(8%1%)SASBASAIMSEPS13,5,8,,,,,,(4,+0171kg);,(26,-1126kg;52,+1105kg),(,),QT(-4.4)(-3.5);QT30,(4.3%)(5.5%),QT,122Evaluationandanalysisofdrug2useinhospitalsofChina2005Vol.5No.2©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.,EPS,,QT,,,SGAEPS2222+++++++++++++++++++++++++QTc++++++++++++++++++P+P+3P+3P+3(?)(?)(?)P+(?)++++++:3;(?);;+;++;+++4[3,10,15]P4502D63A4,,,,,2,,,EPSQT,,[1]AiharaK,ShimadaJ,MiwaT,etal.ThenovelantipsychoticaripirazoleisapartialagonistatshortandlongisoformsofD2receptorslinkedtotheregulationofadenylylcyclaseactivityandprolactinrelease[J].BrainResearch,2004,1003:9.[2]BourinM,AubyP,SwaninkR,etal.Aripiprazoleversushaloperidolformaintainedtreatmenteffectinacutemania[M].In:NewResearchAbstractsofthe156thAnnualMeetingoftheAmericanPsychiatricAssociation;SanFrancisco,Calif.2003May20,AbstractNR467:175.[3]LiebermanJ,CarsonWH,SahaAR,etal.Meta-analysisoftheefficacyofaripirazoleinschizophrenia[J].IntJNeuropsychupharmacol,2002,5(suppl1):S186.[4]MarderSR,McQuadeRD,StockE,etal.Aripirazoleinthetreatmentofschizophrenia:safetyandtolerabilityinshort-termplacebo-controlledtrials[J].SchizophrRes,2003,61:123.[5]LiebermanJ.Aripirazole,TheAmericanPsychiatricPublishingTextbookofPsychopharmacology[M].ThirdEdition.AmericanPsychiatricPublishing,Inc.2004:487493.[6]McQuadeRD,JodyD,KujawaMJ,etal.Long-termweighteffectsofaripiprazoleversusolanzapine[M].In:NewResearchAbstractsofthe156thAnnualMeetingoftheAmericanPsychiatricAssociation.SanFrancisco,Calif.2003May19,AbstractNR231:86.[7]PotkinSG,SahaAR,KujawaMJ,etal.Aripiprazole,anantipsychoticwithanovelmechanismofaction,andrisperidonevsplaceboinpatientswithschizophreniaorschizoaffectivedisorder[J].ArchGenPsychiatry,2003,60:681.[8]DavisKL,KahnRS,KoG,etal.Dopamineinschizophrenia:areviewandreconceptualization[J].AmJPsychiatry,1991,148:1474.[9]BurnsKD,MolskiTF,XuC,etal.Aripirazole,anovelantipsychotic,isahighaffinitypartialagonistathumandopamineD2receptors[J].JPharmacolExpTher,2002,302:381.[10]DeDeynP,JesteD,AubyP,etal.AripiprazoleforPsychosisofAlzheimersDisease[poster][M].Presentedatthe16thAnnualMeetingoftheAmericanAssociationforGeriatricPsychiatry,Honolulu,Hawaii,March14,2003.[11]FleischhackerWW.Newdevelopmentsinthepharmaco2therapyofschizophrenia[J].JNeuralTransm,2003,64(Suppl):105.[12]JordanS,KoprivicaV,ChenR,etal.Theantipsychoticaripirazoleisapotent,partialagonistatthehuman5-HT1Areceptor[J].EurJPharmacol,2002,441:137.[13]KatherineA,Lyseng-Williamson,CarolineM,etal.Ari2pirazole:inacutemaniaassociatedwithbipolarIdisorder,adisdrugprofile[J].CNSDrugs,2004,18(6):367.[14]KujawaM,SahaAR,IngenitoGG,etal.Aripirazoleforlong-termmaintenancetreatmentofschizophrenia(abstract)[J].IntJNeuropsychopharmacol,2002,5(suppl1):S186.[15]KaneJM,CarsonWH,SahaAR,etal.Efficacyandsafetyofaripiprazoleandhaloperidolvsplaceboinpatientswithschizophreniaandschizoaffectivedisorder[J].JClinPsychiatry,2002,63:763.(:2005-02-15)200552123©1995-2005TsinghuaTongfangOpticalDiscCo.,Ltd.Allrightsreserved.