自主神經(jīng)系統(tǒng)是指調(diào)節(jié)內(nèi)臟功能的神經(jīng)裝置

1、Chapter 6 Antispasmodics and muscular relexants,Pharmacodynamic Mechanism,,自主神經(jīng)系統(tǒng)是指調(diào)節(jié)內(nèi)臟功能的神經(jīng)裝置，也可稱為植物性神經(jīng)系統(tǒng)或內(nèi)臟神經(jīng)系統(tǒng)。實際上，自主神經(jīng)系統(tǒng)還是受中樞神經(jīng)系統(tǒng)控制的，并不是完全獨立的，自主神經(jīng)系統(tǒng)僅支配內(nèi)臟的傳出神經(jīng)，不包括傳入神經(jīng)。Autonomic nervous system is the neural regulati

2、on 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 nervou

3、s system only control visceral efferent nerve, excluding afferent nerve.,The biosynthesis of acetylcholine,,AChE,,,Receptor,E,,,Muscarinic receptor blocking agents：Atropa belladonna alkaloids ：atropine，scopolamine，aniso

4、damine，anisodineN1 receprot blocking agents：美卡拉明，六甲溴銨N2 receprot blocking agents,Anticholinergic drugs,Atropine sulphate,tropine 有3個手性中心，內(nèi)消旋不產(chǎn)生旋光性tropic acid ：Vitali反應一個手性中心，S(-)毒性和活性都大，臨床用(+)，旋光度不得超過0.4叔

5、胺，堿性較強，pKa為9.8，水溶液可使酚酞呈紅色酯鍵：pH3.5-4.0穩(wěn)定，堿性下分解成莨菪醇和消旋莨菪酸注射液注意調(diào)Ph .加1％氯化鈉作為穩(wěn)定劑采用硬質(zhì)中性玻璃 注意滅菌溫度4. 用途：對于M1和M2受體均有作用，用作解痙，散瞳和有機磷中毒的解救 等。毒性大。,1,2,3,4,5,6,*,,Scopolamine bromide,,天然品654-1，合成品654-2

6、特點：興奮呼吸中樞，抑制大腦皮質(zhì)用途：鎮(zhèn)靜藥，全麻前給藥，暈動病，震顫麻痹，狂躁型精神病，有機磷中毒及感染性休克。,,環(huán)氧基：,脂溶性,polarity,中樞作用強于阿托品,,,特點：山莨宕醇（不對稱）藥用（-），但（+）也可,Anisodamine bromide,,6-羥基：極性大，難以透過血腦屏障，中樞作用弱口服吸收差，注射尿排迅速,用途：感染性中毒休克，血管性疾病，各種神經(jīng)痛及平滑肌痙攣等。,,Scopolamine

7、butylbromide,（1S,3S,5R,6R,7S,8S）-6,7-環(huán)氧-8-丁基-3（S）-環(huán)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 scop

8、olamine 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 admini

9、stration。,SAR of M receptor antagonists,Aminoethanol ester be considered as the basic activity structure.,4．大多數(shù)強效抗膽堿藥物中，氨基部分通常為季銨鹽或叔胺結(jié)構(gòu)。它們本身為N正離子或與酸成鹽后形成N正離子，與M受體的負離子部位結(jié)合，對形成藥物-受體復合物起重要作用。N上取代烷基通常以甲基、乙基、丙基或異丙基為好，,5．環(huán)取代基到

10、氨基氮原子之間的距離，以n=2為最好，碳鏈長度一般在2~4個碳原子之間，再延長碳鏈則活性降低或消失?？傊?，簡單地說，M膽堿受體拮抗劑的分子結(jié)構(gòu)是由一定長度的結(jié)構(gòu)單元（例如酯基等）將一端的正離子基團和另一端的環(huán)狀基團連接起來，分子中存在羥基利于與受體的結(jié)合。,發(fā)展方向,M1受體拮抗劑,Central musclar relaxants,Within the central block the neurons transmission

11、impulse in the central nervous system,relax the skeletal muscle. Chlorzoxazone: for the treatment of skeletal muscle diseases and muscle pain.,氯化琥珀膽堿 Suxamethonium chloride,二氯化2,2`-[(1,4-二氧-1,4-亞丁基)雙(氧)]雙[N,N,N-三甲基乙銨]

12、二水合物，又名司可林      1．雙酯鍵：固體穩(wěn)定，水中水解，堿性下極易水解。體內(nèi)代謝水解。-----注射劑應注意冷藏或制成粉針-----注射液丙二醇作溶液，穩(wěn)定性好。-----不能與堿性藥物合用，如與硫噴妥鈉。      2．雜質(zhì)限量檢查：膽堿，琥珀酸和琥珀酸單酯 用途：本

13、品為去極化型外周骨骼肌松弛劑，持續(xù)時間較短。常用于氣管內(nèi)插管手術(shù)的全身麻醉,4,1,2,3,2`,2,阿曲庫銨苯磺酸鹽,Symmetric 1 – benzyltetrahydro Isoquinoline drugs, double amine structure 4 chiral carbons, a mixture of isomers Represents the Hofmann elimination and est

14、er 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-depolarizi