神经系统药理魏尔清(抗帕金森病药.ppt

1、Part 10Drugs Treating Parkinson Disease and Alzheimer DiseaseLevodopa and related drugsCholinoceptor antagonistsDrugs treating dementiaDrugs for treatment of Parkinson disease(PD)Levodopa and related drugsCholinoceptor antagonistsParkinson disease and therapeutic drugsRigidity:Rigidity:one of the co

2、mmon one of the common symptoms of PDsymptoms of PDTremor:Tremor:one of the one of the common symptoms of PDcommon symptoms of PDPyramidal and Pyramidal and extrapyramidal pathwaysextrapyramidal pathwaysStriatumStriatum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Su

3、bstantiaSubstantia nigronigro-striatum striatum dopaminergicdopaminergic pathwaypathway is involved in is involved in PD pathogenesisPD pathogenesisParkinson diseaseParkinson diseaseDopaminergic neuron Dopaminergic neuron degeneration in degeneration in substantiasubstantia nigronigro and and striat

4、umstriatumNormalNormalPDControlProduce dopamineDopamineDopamineAcetylcholineAcetylcholineAbnormal balance of DA/Abnormal balance of DA/AChACh neuronal functions neuronal functions in extrapyramidal system of Parkinson diseasein extrapyramidal system of Parkinson diseaseLevodopaLevodopaMuscarinicMusc

5、arinic antagonistsantagonistsNormalNormalParkinson diseaseParkinson disease(-)(-)injuredinjuredrelatively relatively potentiatedpotentiatedPD:PD:GABA GABA HD:HD:GABA GABA (+(+)(-)(-)(-)(-)(+(+)(-)(-)(-)(-)(-)(-)Levodopa and related drugsLevodopa,L-dopa 左左左左旋多巴旋多巴旋多巴旋多巴Drugs for treatment of Parkinso

6、n diseaseLevodopaLevodopaDopamineDopamineLevodopa1.ADME1.ADME Penetrating into the brain,transformed to DA or NE(less)Penetrating into the brain,transformed to DA or NE(less)Distributed in peripheral tissue(most)Distributed in peripheral tissue(most)2.Effects and uses2.Effects and uses Parkinson dis

7、ease:Parkinson disease:decreases the rigidity,tremors,and other decreases the rigidity,tremors,and other symptomssymptoms3.Adverse effects3.Adverse effects(1)CNS:(1)CNS:abnormal involuntary;hallucinations;abnormal involuntary;hallucinations;etcetc.(2)GI:(2)GI:nausea,vomiting,nausea,vomiting,etcetc.(

8、3)CVS:(3)CVS:hypotension,arrhythmia,hypotension,arrhythmia,etcetc.Drugs for treatment of Parkinson diseaseInhibitors of aromatic L-amino acid decarboxylaseCarbidopa 卡比多巴卡比多巴卡比多巴卡比多巴can not cross BBB,but can inhibit peripheral can not cross BBB,but can inhibit peripheral dopamine synthesis.dopamine s

9、ynthesis.increases availability of increases availability of levodopalevodopa to the CNS and to the CNS and decreases peripheral effectsdecreases peripheral effectsDrugs for treatment of Parkinson diseaseLevodopaLevodopa alone aloneLevodopaLevodopa +CarbidopaCarbidopaOther drugs1.DA receptor agonist

10、sBromocriptine 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Drugs for treatment of Parkinson disease2.MAO inhibitors decreasing DA metabolism in the CNSdecreasing DA metabolism in the CNSSelegiline 司来吉兰司来吉兰司来吉兰司来吉兰RasagilineRasagil

11、ine 雷沙吉兰雷沙吉兰雷沙吉兰雷沙吉兰3.COMT inhibitorsdecreasing DA metabolism in the CNSdecreasing DA metabolism in the CNSNitecapone 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increasing DA releaseincreasing DA releaseDrugs for treatment of Parkinson diseaseMuscarinic antagonistsTrihexyphenidyl（苯海索苯海索苯海索苯海索，arta

12、neartane,安坦安坦安坦安坦）Decreasing CNS cholinergic functionsAdjuvant of Parkison disease treatmentDrugs for treatment of Parkinson diseaseDrugs for treatment of dementia(Alzheimer and related diseases)Anticholinesterase drugsCholinoceptor agonistsNeurotrophic factor-like drugsAnticholinesterase drugs Tarc

13、rineTarcrine 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Cholinoceptor agonists XanomelineXanomeline 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Neurotrophic factor-like drugs AIT 082AIT 082 PropentofyllinePropentofylline 丙戊茶碱丙

14、戊茶碱丙戊茶碱丙戊茶碱Drugs for treatment of dementiaPathological characteristics of ADAtrophy of the brainAtrophy of the brainSenile plaquesSenile plaquesNeurofibrillaryNeurofibrillary tanglestanglesSenile plaquesSenile plaques and neurofibrillaryneurofibrillary tangles tanglesRegions related to neuronal inju

15、ryRegions related to neuronal injuryImportance of Importance of AChACh system system 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