115-79-7

• 常用中文名：安贝氯铵
• 常用英文名：AI3-22370
• CAS号：115-79-7
• 分子式：C₂₈H₄₂Cl₄N₄O₂
• 分子量：608.47100
• 相关类别： 原料药 神经系统用药 拟胆碱药
• 发布时间：2018-05-15 08:00:00
• 更新时间：2024-01-02 11:23:59
• 氯化氨苯诺铵(WIN 8077)是一种口服活性和可逆的乙酰胆碱酯酶(AChE)抑制剂,具有高亲和力。氯化铵抑制人乙酰胆碱酯酶的IC50值为0.7nM(hAChE)[1][2]。

名称

• 中文名: 安贝氯铵
• 英文名: ambenonium chloride
• 中文别名: 安贝氯胺
• 英文别名: Ambestigmin; EINECS 204-107-5; Mytelase; Ambenonium Dichloride; MFCD00153762

物化性质

• 熔点: 196-199°
• 分子式: C₂₈H₄₂Cl₄N₄O₂
• 分子量: 608.47100
• 精确质量: 606.20600
• PSA: 58.20000
• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:2

  3.氢键受体数量:4

  4.可旋转化学键数量:14

  5.互变异构体数量:3

  6.拓扑分子极性表面积58.2

  7.重原子数量:38

  8.表面电荷:0

  9.复杂度:614

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:3

生物活性

• 描述: 氯化氨苯诺铵(WIN 8077)是一种口服活性和可逆的乙酰胆碱酯酶(AChE)抑制剂,具有高亲和力。氯化铵抑制人乙酰胆碱酯酶的IC50值为0.7nM(hAChE)[1][2]。
• 相关类别:
  研究领域 >> 其他
  信号通路 >> 神经信号通路 >> 疼痛
• 靶点:

  Acetylcholinesterase:0.7 nM (IC50)

  Acetylcholinesterase:0.12 nM (Ki)

  Butyrylcholinesterase:7 μM (IC50)

• 体外研究: 氯化铵以快速可逆的方式抑制乙酰胆碱酯酶(AChE),并显示出对hAChE的强烈抑制,抑制常数Ki为0.12nM[1]。氯化铵对BChE具有抑制作用,IC50值为7μM(hBChE)[2]。
• 体内研究: 氯化铵(6 mg/kg；p.o；每日；30-60天)在长期给药时对神经肌肉传递产生不良影响,并在重症肌无力小鼠模型中诱导对刺激的超敏反应[3]。氯化铵(6 mg/kg；p.o；每日；14 d)可减少运动终板中的AChR数量[3]。动物模型：患有重症肌无力的雌性Sprague-Dawley大鼠(体重250g)[3]剂量：6mg/kg给药：口服灌胃；每日的14、30、60、90、360天(提前24小时停止给药)结果：在第30-60天,大鼠的一般活动减少,对刺激过敏,但这些行为在第90天消失。导致突触后皱褶变性和简化,突触裂变宽,突触后小泡数量增加,第360天突触后膜中的AChR数量减少。
• 参考文献:

  [1]. Hodge AS, et al. Ambenonium is a rapidly reversible noncovalent inhibitor of acetylcholinesterase, with one of the highest known affinities. Mol Pharmacol. 1992 May. 41(5):937-42.

  [2]. Komloova M, et al. Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors--implications for early myasthenia gravis treatment. Bioorg Med Chem Lett. 2011 Apr 15. 21(8):2505-9.

  [3]. Hazama R, et al. Effects of long-term administration of ambenonium chloride on motor end-plate fine structure and acetylcholine receptor in rat. J Neurol Sci. 1981 Jul. 51(1):69-79.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : BR9808000 CHEMICAL NAME : Ammonium, (oxalylbis(iminoethylene))bis((o-chlorobenzyl)diethyl -, dichloride CAS REGISTRY NUMBER : 115-79-7 LAST UPDATED : 198910 DATA ITEMS CITED : 8 MOLECULAR FORMULA : C28-H42-Cl2-N4-O2.2Cl MOLECULAR WEIGHT : 608.54 WISWESSER LINE NOTATION : R1K2&2&2MVVM2K2&2&1R &G 2 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,132,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,132,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2720 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,132,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 145 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,132,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 6300 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 128,307,1960 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3700 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,132,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1510 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,132,1982 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 1600 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - fasciculations Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Lungs, Thorax, or Respiration - dyspnea REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 115,185,1955

安全

• 危害码 (欧洲): T+
• 风险声明 (欧洲): R28
• 安全声明 (欧洲): S28;S45;S36/S37
• 危险品运输编码: UN 2811 6.1/PG 2