治疗中枢神经系统退行性疾病药物

AgentsforParkinson’sDisease治疗中枢神经系统退行性疾病药物17Parkinson’sDisease（PD）:Originallydescribedin1817byBritishphysician,JamesParkinson,whocalledit“theshakingpalsy.About1960thediseasewastracedtothelossofdopamine-producingneuronsinthesubstantianigraSymptomsofPD:Tremblingofhands,arms,legs,jawandfaceStiffnessofthearms,legsandtrunkSlownessofmovementPoorbalanceandcoordination第1节抗帕金森氏病药Anti-PDDrugs1.MechanismofPDDopamine：InhibitionACh:Excitation1.+DA2.Anti-Ach3.StimulateD-RSlowFastL-aminoacidtransporteronBBB?D1-3,whichisimportantforPD?二、拟多巴胺类药物LEVODOPAAromaticL-aminoaciddecarboxylase（AADC)ActiveIntoBloodDopmineBBBActiveCNSDopamine(insideoroutsideofC?)CarbidopaBenserazide帕金宁,心宁美IndicationsofL-DopaAlltypesofPD,exceptforthoseinducedbyChlorpromazineAntagonistofD2D2isresponsibleforPDSideEffectsofLevodopa1.GastrointestinalEffectsDirectstimulationStimualtionofthechemoreceptortriggerzonelocatedinthebrainstembyDADomperidone(吗叮啉）-AntagonistofD2Toincreasethedoseslowly2.CardiovascularEffectsIncreasedcatecholamineformation-cardiacarrhythmiaBetaantagonistLongPeriods1.Dyskinesia:Amovementdisorderwhichconsistsofeffectsincludingdiminishedvoluntarymovementsandthepresenceofinvoluntarymovements,similartoticsorchorea.为什么初期治疗没有？2.On-offresponse3.AdversementaleffectsDrugInteractionsVitaminB6:Awater-solublevitaminandispartofthevitaminBcomplexgroup.Pyridoxalphosphate(PLP)istheactiveformandisacofactorinmanyreactionsofaminoacidmetabolism,includingtransamination,deamination,anddecarboxylation.PLPalsoisnecessaryfortheenzymaticreactiongoverningthereleaseofglucosefromglycogen.Selegiline:InhibitorofMAO-BinCNSNitecapone:InhibitorofCOMToutsideofCNSTocapone:InhibitorofCOMTofwholebodyBromocriptineLisuridePergolide3.AgonistofDRDR-D1-5D2AgonistofD2AD?4.AgentstoincreasethereleaseofDA三、抗胆碱药CholinoceptorantagonistsBenzhexolBenzatropineAtropineScopolamine?1.甲磺酸培高利特：美韩发现心血管不良反应，中国如何撤药？2.美多巴，心宁美的组方原理？3.为什么美多巴之类用到最后，还是无效？4.开关现象？如何调整给药方案？5.Levodopa是否可用于精神疾病患者？闭角型青光眼患者？消化性溃疡患者?