第8章抗胆碱酯酶药Chapter8AnticholinesteraseDrugs中山医学院林明栋第一节第一节胆碱酯酶胆碱酯酶水解过程结合裂解水解EsteraticsiteAnionicsite脂解部位阴离子部位AcetateAc-serinehydrolysedAcetyl-grouptransferredtoserine-OHAcetylcholinebindsEsteraticsiteAnionicsite结合裂解水解第二节抗胆碱酯酶药第二节抗胆碱酯酶药(anticholinesteraseagents)(anticholinesteraseagents)非共价结合的抑制药氨甲酰类抑制药有机磷化合物易逆性抗AChE药难逆性抗AChE药OONOONneostigminecholinecarbamyl-serinehydrolysed(slow)acetyl-grouptransferredtoserine-OHAChac-serinehydrolysed(fast)acetateNHONNHOHisSerGluCOONNHOHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOOphospatetransferredto-NOHreactivationAChEreactivateddyfloscarbamyltransferredtoserine-OHnospontaneoushydrolysisesteraticsitephosphorylatedenzymepralidoximeNNHOHisSerGluCOOOONNNHisSerGluCOOOOONNOOOONNOONFPHOOPrOPrOPrOPrHOPOHONNOPrOPrHOPOHONNONNOPHOOPrCABAChEanionicsiteOONNOONOONneostigminecholinecarbamyl-serinehydrolysed(slow)acetyl-grouptransferredtoserine-OHAChac-serinehydrolysed(fast)acetateNHONNHOHisSerGluCOONNHOHisSerGluCOONNHOHisSerGluCOONNHOHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOONNHisSerGluCOOphospatetransferredto-NOHreactivationAChEreactivateddyfloscarbamyltransferredtoserine-OHnospontaneoushydrolysisesteraticsitephosphorylatedenzymepralidoximeNNHOHisSerGluCOONNHOHisSerGluCOOOONNNHisSerGluCOONNHisSerGluCOOOOONNOOOONNOONFPHOOPrOPrOPrOPrHOPOHONNOPrOPrHOPOOPrOPrHOPOHONNONNOPHOOPrCABAChEanionicsiteOONNFig.8-1TheinteractionsofAChEwithacetylcholine(A),reversibleanticholinesterasedrugs(B)andirreversibleanticholinesteraseagents(C).anticholinesteraseagentsanticholinesteraseagents非共价结合的抑制药依酚氯铵（edrophonium）他克林（tacrine）多奈哌齐（donepezil）anticholinesteraseagentsanticholinesteraseagents氨甲酰类抑制药新斯的明（neostigmine）吡斯的明（pyridostigmine）地美溴铵（demecarium）利凡斯的明（rivastigmine）易逆性抗易逆性抗AChEA...
