自主神经系统是指调节内脏功能的神经装置共享精品课件

Chapter 6 Antispasmodics and muscular relexants Pharmacodynamic Mechanism 自主神经系统是指调节内脏功能的神经装置，也可称为植物性 神经系统或内脏神经系统。实际上，自主神经系统还是受中枢 神经系统控制的，并不是完全独立的，自主神经系统仅支配内 脏的传出神经，不包括传入神经。 Autonomic nervous system is the neural regulation of visceral function devices, may also be known as the plant or visceral nervous system. In fact, the autonomic nervous system is controlled by the central nervous system and is not fully independent. Autonomic nervous system only control visceral efferent nerve, excluding afferent nerve. The biosynthesis of acetylcholine AChE Receptor E receptordistributionPhysiological function Agonistsantagonists MM1大脑脑皮质质、海马马、纹纹状体 、周围围神经节经节和分泌腺体 与传递传递神经经元的兴兴 奋奋冲动动有关、调节调节 大脑脑的各种功能，并 调节调节汗腺和消化腺 体的分泌 治疗疗早老性痴 呆 治疗疗消化道溃疡溃疡 M2中枢神经经系统较统较低脑脑区和 心脏脏等周围围效应应器组织组织 引起心肌收缩缩力减弱 、心率降低、传导传导 减慢 有可能用于治 疗疗冠心病和心 动过动过速 治疗疗心动动徐缓缓性 心率失常 M3腺体和平滑肌血管平滑肌舒张张、胃 肠肠道和膀胱平滑肌收 缩缩、括约约肌松弛、 瞳孔缩缩小、腺体分泌 增加 治疗痉挛疗痉挛 性血 管病、手术术后 腹气胀胀、尿潴 溜 治疗疗慢性阻塞性 呼吸道疾病、尿 失禁 M4腺体和平滑肌抑制钙钙离子通道缺乏特异性配基 M5大脑脑孤儿受体缺乏特异性配基 NN1神经节经节释释放乙酰酰胆碱治疗疗早老性痴呆治疗疗高血压压 N2神经经肌肉接头头松弛骨骼肌 Muscarinic receptor blocking agents： Atropa belladonna alkaloids ：atropine，scopolamine ，anisodamine，anisodine N1 receprot blocking agents：美卡拉明，六甲溴铵 N2 receprot blocking agents Anticholinergic drugs Atropine sulphate 1.tropine 有3个手性中心，内消旋不产生旋光性 tropic acid ：Vitali反应 一个手性中心，S(-)毒性和活性都大，临床用(+)，旋光度不得超过0.4 2.叔胺，碱性较强，pKa为9.8，水溶液可使酚酞呈红色 3.酯键：pH3.5-4.0稳定，碱性下分解成莨菪醇和消旋莨菪酸 注射液注意调Ph .加1氯化钠作为稳定剂 采用硬质中性玻璃 注意灭菌温度 4. 用途：对于M1和M2受体均有作用，用作解痉，散瞳和有机磷中毒的解救 等。毒性大。 1 2 3 4 5 6 * Scopolamine bromide 天然品654-1，合成品654-2 特点：兴奋呼吸中枢，抑制大脑皮质 用途：镇静药，全麻前给药，晕动病，震颤麻痹 ，狂躁型精神病，有机磷中毒及感染性休克。 环氧基 ： 脂溶性 polarity 中枢作用强于阿托品 特点：山莨宕醇（不对称 ） 药用（-），但（+）也可 Anisodamine bromide 6-羟基： 1. 极性大，难以透过血 脑屏障，中枢作用弱 2. 口服吸收差，注射尿 排迅速 用途：感染性中毒休克 ，血管性疾病，各种神 经痛及平滑肌痉挛等。 Scopolamine butylbromide （1S,3S,5R,6R,7S,8S）-6,7-环氧-8-丁基-3（S）-环氧托烷基托 哌溴化物 1. soluble in chloroform and water, slightly soluble in ethanol. 2. has the characteristics reaction of tropic acid. 3. quaternary ammonium compounds of scopolamine with the weak central nervous system function and being peripheral anticholinergic drugs for spasticity, such as the gastrointestinal tract. 4. Oral non-absorption, intramuscular injection or intravenous administration。 SAR of M receptor antagonists Aminoethanol ester be considered as the basic activity structure. 4大多数强效抗胆碱药物中，氨基部分通常为季铵盐或叔胺 结构。它们本身为N正离子或与酸成盐后形成N正离子，与M 受体的负离子部位结合，对形成药物-受体复合物起重要作用 。N上取代烷基通常以甲基、乙基、丙基或异丙基为好， 5环取代基到氨基氮原子之间的距离，以n=2为最好，碳链 长度一般在24个碳原子之间，再延长碳链则活性降低或消 失。 总之，简单地说，M胆碱受体拮抗剂的分子结构是由一定长 度的结构单元（例如酯基等）将一端的正离子基团和另一端 的环状基团连接起来，分子中存在羟基利于与受体的结合。 发展方向 M1受体拮抗剂 Central musclar relaxants Within the central block the neurons transmission impulse in the central nervous system,relax the skeletal muscle. Chlorzoxazone: for the treatment of skeletal muscle diseases and muscle pain. 氯化琥珀胆碱 Suxamethonium chloride 二氯化2,2-(1,4-二氧-1,4-亚丁基)双(氧)双N,N,N-三甲基乙铵二水合物 ，又名司可林 1双酯键：固体稳定，水中水解，碱性下极易水解。体内代谢水解 。 -注射剂应注意冷藏或制成粉针 -注射液丙二醇作溶液，稳定性好。 -不能与碱性药物合用，如与硫喷妥钠。 2杂质限量检查：胆碱，琥珀酸和琥珀酸单酯 用途： 本品为去极化型外周骨骼肌松弛剂，持续时间较短。 常用于气管内插管手术的全身麻醉 4 1 2 3 2 2 阿曲库铵苯磺酸盐 Symmetric 1 benzyltetrahydro Isoquinoline drugs, double amine structure 4 chiral carbons, a mixture of isomers Represents the Hofmann elimination and ester degradation metabolism, slight side effects With androgenic nucleus, but no androgen activity. Both ring A and ring D with the structure of acetylcholine-like fragment Drug for major surgery Steroid non-depolarizing neuromuscular blocker 1，1-3a，17b-双-（乙酰氧基）-5a-雄甾烷-2b，16b-二基 双-1-甲基哌啶鎓二溴化物 泮库溴铵 cluDMU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS#+8hqzHQZ- 7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ -7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ- 7gpxGPY)6enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOX*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOX*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ- 7gpxGPY)6enwFOX*4dmvEMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envENW*4cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOX*4dmvEMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envENW*4cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOX*4dmvEMV&3cltCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envENW*4cluDMV%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOX*4dmvEMV&3cltCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envENW*4cluDMV%2bktBKT$1airAJS!+8hqzIQZ- 7gpxGPY)6enwFOX*4dmvEMV&3cltCLU%2ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5envNW*4dmuDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5dmvENW&3cluDLU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFNW*4dmuDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5dmvENW&3cluDLU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFNW*4dmuDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW&3cluDLU%2bksBKT$19irAJS#+8hqzHQZ- 7goxGPY)5enwFOW*4dmuDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW&3cluDLU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmuDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDLU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDLU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3bktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bksBKT$19irAJS#+8hqzHQZ- 7goxGPY)5enwFOW*4dmvDMV&3cktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bksBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU$1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$19irAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$19irAJS#+8hqzHQZ- 7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBJS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS#+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09iqzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzHQZ- 7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+7gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzirAJS!+8hqzHQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQY)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ- 7goxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxFOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)5enwFOW*4dmvDMV&3cktCLU%1ajsBKS!09irzIR#+8gpyHQZ)6foxGOX(5emvENW*3cluDMU%2bktBKT$1airAJS!+8hqzIQZ-7gpxGPY)6enwFOW*4dmvDMV&3ck