神经系统药理魏尔清(抗帕金森病药.ppt

神经系统药理魏尔清(抗帕金森病药.ppt

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Part10DrugsTreatingParkinsonDiseaseandAlzheimerDiseaseLevodopaandrelateddrugsCholinoceptorantagonistsDrugstreatingdementiaDrugsfortreatmentofParkinsondisease（PD）LevodopaandrelateddrugsCholinoceptorantagonistsParkinsondiseaseandtherapeuticdrugsRigidity:

Rigidity:

oneofthecommononeofthecommonsymptomsofPDsymptomsofPDTremor:

Tremor:

oneoftheoneofthecommonsymptomsofPDcommonsymptomsofPDPyramidalandPyramidalandextrapyramidalpathwaysextrapyramidalpathwaysStriatumStriatum黑质黑质黑质黑质-纹状体通路纹状体通路纹状体通路纹状体通路中脑中脑中脑中脑-皮层通路皮层通路皮层通路皮层通路结节结节结节结节-漏斗通路漏斗通路漏斗通路漏斗通路SubstantiaSubstantianigronigro-striatumstriatumdopaminergicdopaminergicpathwaypathwayisinvolvedinisinvolvedinPDpathogenesisPDpathogenesisParkinsondiseaseParkinsondiseaseDopaminergicneuronDopaminergicneurondegenerationindegenerationinsubstantiasubstantianigronigroandandstriatumstriatumNormalNormalPDControlProducedopamineDopamineDopamineAcetylcholineAcetylcholineAbnormalbalanceofDA/AbnormalbalanceofDA/AChAChneuronalfunctionsneuronalfunctionsinextrapyramidalsystemofParkinsondiseaseinextrapyramidalsystemofParkinsondiseaseLevodopaLevodopaMuscarinicMuscarinicantagonistsantagonistsNormalNormalParkinsondiseaseParkinsondisease（-）（-）injuredinjuredrelativelyrelativelypotentiatedpotentiatedPD:

PD:

GABAGABAHD:

HD:

GABAGABA（+（+）（-）（-）（-）（-）（+（+）（-）（-）（-）（-）（-）（-）LevodopaandrelateddrugsLevodopa,L-dopa左左左左旋多巴旋多巴旋多巴旋多巴DrugsfortreatmentofParkinsondiseaseLevodopaLevodopaDopamineDopamineLevodopa1.ADME1.ADMEPenetratingintothebrain,transformedtoDAorNE（less）Penetratingintothebrain,transformedtoDAorNE（less）Distributedinperipheraltissue（most）Distributedinperipheraltissue（most）2.Effectsanduses2.EffectsandusesParkinsondisease:

Parkinsondisease:

decreasestherigidity,tremors,andotherdecreasestherigidity,tremors,andothersymptomssymptoms3.Adverseeffects3.Adverseeffects

（1）CNS:

（1）CNS:

abnormalinvoluntary;hallucinations;abnormalinvoluntary;hallucinations;etcetc.

（2）GI:

（2）GI:

nausea,vomiting,nausea,vomiting,etcetc.（3）CVS:

（3）CVS:

hypotension,arrhythmia,hypotension,arrhythmia,etcetc.DrugsfortreatmentofParkinsondiseaseInhibitorsofaromaticL-aminoaciddecarboxylaseCarbidopa卡比多巴卡比多巴卡比多巴卡比多巴cannotcrossBBB,butcaninhibitperipheralcannotcrossBBB,butcaninhibitperipheraldopaminesynthesis.dopaminesynthesis.increasesavailabilityofincreasesavailabilityoflevodopalevodopatotheCNSandtotheCNSanddecreasesperipheraleffectsdecreasesperipheraleffectsDrugsfortreatmentofParkinsondiseaseLevodopaLevodopaalonealoneLevodopaLevodopa+CarbidopaCarbidopaOtherdrugs1.DAreceptoragonistsBromocriptine溴隐亭溴隐亭溴隐亭溴隐亭Pergolide培高利特培高利特培高利特培高利特PramiperolePramiperole普拉克索普拉克索普拉克索普拉克索RopiniroleRopinirole罗平尼咯罗平尼咯罗平尼咯罗平尼咯DrugsfortreatmentofParkinsondisease2.MAOinhibitorsdecreasingDAmetabolismintheCNSdecreasingDAmetabolismintheCNSSelegiline司来吉兰司来吉兰司来吉兰司来吉兰RasagilineRasagiline雷沙吉兰雷沙吉兰雷沙吉兰雷沙吉兰3.COMTinhibitorsdecreasingDAmetabolismintheCNSdecreasingDAmetabolismintheCNSNitecapone硝替卡朋硝替卡朋硝替卡朋硝替卡朋4.Amantadine金刚烷胺金刚烷胺金刚烷胺金刚烷胺increasingDAreleaseincreasingDAreleaseDrugsfortreatmentofParkinsondiseaseMuscarinicantagonistsTrihexyphenidyl（苯海索苯海索苯海索苯海索，artaneartane,安坦安坦安坦安坦）DecreasingCNScholinergicfunctionsAdjuvantofParkisondiseasetreatmentDrugsfortreatmentofParkinsondiseaseDrugsfortreatmentofdementia（Alzheimerandrelateddiseases）AnticholinesterasedrugsCholinoceptoragonistsNeurotrophicfactor-likedrugsAnticholinesterasedrugsTarcrineTarcrine他克林他克林他克林他克林HuperzineHuperzine石杉碱甲（哈伯因）石杉碱甲（哈伯因）石杉碱甲（哈伯因）石杉碱甲（哈伯因）GalantamineGalantamine加兰他敏加兰他敏加兰他敏加兰他敏CholinoceptoragonistsXanomelineXanomeline占诺美林占诺美林占诺美林占诺美林MilamelineMilameline米拉美林米拉美林米拉美林米拉美林Neurotrophicfactor-likedrugsAIT082AIT082PropentofyllinePropentofylline丙戊茶碱丙戊茶碱丙戊茶碱丙戊茶碱DrugsfortreatmentofdementiaPathologicalcharacteristicsofADAtrophyofthebrainAtrophyofthebrainSenileplaquesSenileplaquesNeurofibrillaryNeurofibrillarytanglestanglesSenileplaquesSenileplaquesandneurofibrillaryneurofibrillarytanglestanglesRegionsrelatedtoneuronalinjuryRegionsrelatedtoneuronalinjuryImportanceofImportanceofAChAChsystemsystem淀粉样多肽（淀粉样多肽（淀粉样多肽（淀粉样多肽（AA）形成形成形成形成淀粉样多肽淀粉样多肽淀粉样多肽淀粉样多肽细胞外蓄积细胞外蓄积细胞外蓄积细胞外蓄积tautau蛋白蛋白蛋白蛋白细胞内蓄积细胞内蓄积细胞内蓄积细胞内蓄积神经元功能损伤，神经变性神经元功能损伤，神经变性神经元功能损伤，神经变性神经元功能损伤，神经变性痴呆发生痴呆发生痴呆发生痴呆发生炎症反应，氧自由基产生炎症反应，氧自由基产生炎症反应，氧自由基产生炎症反应，氧自由基产生钙平衡失调，细胞功能紊乱钙平衡失调，细胞功能紊乱钙平衡失调，细胞功能紊乱钙平衡失调，细胞功能紊乱遗传异常，环境影响遗传异常，环境影响遗传异常，环境影响遗传异常，环境影响