Anticholinesterases 1. Reversible anticholinesterases 2. reversible anticholinesterases
Anticholinesterases 1. Reversible anticholinesterases 2. Irreversible anticholinesterases
Reversible anticholinesterases anionic site esteratic site H3C-N-CH2-CH2-0-C-CH3 Acetylcholinesterase is the mechanism of terminating Ach effects
• anionic site esteratic site • Acetylcholinesterase is the mechanism of terminating ACh effects Reversible anticholinesterases
酯解部位 阴离子部位 H0-C=0 CCH 乙酸 0 His ho Glu 胆碱酯酶 3) 0 CH3 乙酰化AChE COO ACh与AChE复合物 2) H3C、CH2-CH2-0H H3C CH 胆碱 Action of acetylcholinesterase
Action of acetylcholinesterase
124 286 74 66 203 297 202 337449 442 Acetylcholinese: structure for interaction with substrate
Acetylcholinese: structure for interaction with substrate
Reversible anticholinesterases Neostigmine新斯的明 CH3N—COO N+(CH3)3 Neostigmine新斯的明
Neostigmine 新斯的明 CH3 COO N CH3 N + (CH3)3 Neostigmine 新斯的明 Reversible anticholinesterases
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
Reversible anticholinesterases 2. Clinical uses (1) Myasthenia gravis(重症肌无力): symptomatic treatment, overdose: cholinergic crisis (2) Paralytic ileus and bladder(手术后肠道及膀胱麻 A: post operative abdominal distension and urinary retention (3 )Antidote for nondepolarizing skeletal muscle relaxants poisoning(解除非除极化型肌松药中毒) (4)Paroxysmal superventricular tachycardia(p 发性室上性心动过速)
• 2. Clinical uses • (1) Myasthenia gravis（重症肌无力）: symptomatic treatment, overdose: cholinergic crisis • (2) Paralytic ileus and bladder（手术后肠道及膀胱麻 痹）: post operative abdominal distension and urinary retention • (3) Antidote for nondepolarizing skeletal muscle relaxants poisoning（解除非除极化型肌松药中毒） • (4) Paroxysmal superventricular tachycardia（阵 发性室上性心动过速） Reversible anticholinesterases