Reversible anticholinesterases 1. Pharmacological effects binding to AChE, but slowly hydrolysis inhibiting AChE activity Properties of Effects stronger effect on skeletal muscles AChE(, ACh release, stimulating NM receptor effective on Gl tract and urinary bladder more polar and can not enter CNS relatively ineffective on CVS, glands, eye
• 1. Pharmacological effects • binding to AChE, but slowly hydrolysis • inhibiting AChE activity • Properties of Effects • stronger effect on skeletal muscles • AChE (-), ACh release, stimulating NM receptor • effective on GI tract and urinary bladder • more polar and can not enter CNS • relatively ineffective on CVS, glands, eye Reversible anticholinesterases
NEURON Effect of neostigmine on Acetate Acetyl- AChE choline Choline △A Physostigmine Neostigmine Edrophonium INCREASED INTRACELLULAR RESPONSE
Effect of neostigmine on AChE
可逆性抗胆碱酯酶药酯解部位阴离子部分难逆性抗胆碱酯酶药 活性酶 OPr XO∠ H0-P-Or 新斯的明 HO COO 异氟磷 OP 新斯的明与 磷酰化 AChE NHO-P-0P Nx0C起复合物 不能自动 COO 水解 C00 氨甲酰基丝氨酸酶活性恢复 氨甲酰基转 水解(缓慢) 到丝氨酸羟基 Ho-N OPr 解磷定 HO-P-OPr N C0O机磷转、 CO 运到NOH 二甲胺基甲酰化酶 PrO-FO-N 解磷定与磷酰化AChE复合物 H
(CH3)3 OH N(CH3)2 N。H anionic site esteric site Action of neostigmine on acetylcholinesterase
Action of neostigmine on acetylcholinesterase