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氢溴酸东莨菪碱

氢溴酸东莨菪碱用途

Scopolamine hydrobromide 是高亲和力的 (nM 级别) 毒蕈碱 (muscarinic) 拮抗剂。Scopolamine 可逆抑制 5-HT3 受体反应,IC50 为 2.09 μM。

氢溴酸东莨菪碱名称

[ CAS 号 ]:
114-49-8

[ 中文名 ]:
东莨菪碱氢溴酸盐

[ 英文名 ]:
Scopolamine hydrobromide

[中文别名 ]:

[英文别名 ]:

Beldavrin
Hyosol
Kwells
HYOSCINE
Euscopol
(-)-Scopolamine bromide
TRIPTONE
hyoscine hydrobromide
Atroscine hydrobromide
Isoscopil

氢溴酸东莨菪碱生物活性

[ 描述 ]:

Scopolamine hydrobromide 是高亲和力的 (nM 级别) 毒蕈碱 (muscarinic) 拮抗剂。Scopolamine 可逆抑制 5-HT3 受体反应,IC50 为 2.09 μM。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体

信号通路 >> 神经信号通路 >> 5-HT受体

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 由mAChR

信号通路 >> 神经信号通路 >> mAChR

天然产物 >> 生物碱

研究领域 >> 神经疾病

[ 靶点 ]

5-HT3 Receptor:2.09 μM (IC50)

mAChR

[体外研究]

东莨菪碱在表达5-HT3受体的卵母细胞中的应用在单独施用时不引起反应,但在共同施用2μM5-HT期间引起浓度依赖性的反应抑制。东莨菪碱的pIC50值为5.68±0.05(IC50 =2.09μM,n = 6),Hill斜率为1.06±0.05。这得到Kb为3.23μM。当在5-HT应用期间施用东莨菪碱时也观察到相同的浓度依赖性效应。为了进一步测试5-HT3受体的竞争性结合,用[3H]格拉司琼测量未标记的东莨菪碱的竞争,[3H]格拉司琼是这些受体上已建立的高亲和力竞争性拮抗剂。东莨菪碱与0.6 nM [3H]格拉司琼(~Kd)显示浓度依赖性竞争,平均pKi为5.17±0.24(Ki =6.76μM,n = 3)[1]。

[体内研究]

在组织病理学研究中,大脑的组织学没有显着变化。然而,观察到用仅接受蒸馏水的东莨菪碱预处理的对照小鼠的海马细胞密度降低[2]。与正常组(3.06±0.296)相比,单独使用东莨菪碱可显着提高乙酰胆碱酯酶(AchE)的活性(7.98±0.065; P <0.001)。与正常组(12.82±2.86)相比,用东莨菪碱治疗的动物报告丙二醛(MDA)水平显着增加(34.61±4.85; P <0.01)。与正常组(0.3906±0.02)相比,东莨菪碱处理组显示还原型谷胱甘肽(GSH)水平显着降低(P <0.001; 0.1504±0.03)。与正常组(43.21±3.46)相比,东莨菪碱治疗的大鼠显示β淀粉样蛋白(Aβ1-42)浓度显着增加(P <0.001; 146.2±1.74)[3]。

[激酶实验]

通过将稳定表达5-HT3受体的HEK 293细胞的粗提取物或豚鼠膜制剂在含有10mM HEPES缓冲液（pH7.4）和0.1-1nM的0.5mL培养物中孵育来测量饱和结合（8点）曲线。 3H]格拉司琼或1-10nM [3H] N-甲基 - 环丙胺。通过在含有0.6nM [3H]格拉司琼或0.6nM [3H] N-甲基环丙胺和不同浓度的竞争配体的0.5mL HEPES缓冲液中孵育相同的受体制剂来测定竞争结合（10分）。用1mM喹哌啶或10μM东莨菪碱分别测定非特异性结合。通过过滤到用HEPES缓冲液+ 0.3％聚乙烯亚胺润湿的Whatman GF / B过滤器终止孵育，然后用冰冷的HEPES缓冲液快速洗涤两次。使用具有牛血清白蛋白标准品的Lowry蛋白质测定法计算蛋白质浓度。使用Tri-Carb 2100 TR闪烁计数器[1]测量放射性。

[动物实验]

小鼠[2]将小鼠称重，标记并分成7组，每组5只动物，之后所有动物腹膜内预先注射3mg / kg东莨菪碱。第1-3组给予0.2mL等效剂量的4mg / kg，6mg / kg和8mg / kg的巴戟天提取物，而4-6组给予相同剂量的紫穗槐提取物，第7组给予0.2。连续3天蒸馏水（阴性对照）。大鼠[3]在该研究中使用重180-200g的健康雄性Wistar大鼠（12个月大）。将大鼠分成5组（n = 6 /组）;组I-正常对照，组II-疾病对照（氢溴酸东莨菪碱3mg / kg，ip），组III-东莨菪碱+槲皮素（25mg / kg，po），组IV-标准治疗（东莨菪碱+盐酸多奈哌齐3mg / kg，po）和V-东莨菪碱+槲皮素（25mg / kg，口服）+多奈哌齐（3mg / kg，口服）。 III组，IV组和V组大鼠每24小时间隔给药各自的药物连续14天。 Morris水迷宫，高架迷宫和被动回避范例的采集路线在第14天进行，东莨菪碱（3 mg / kg，ip）在采集后第14天给予除正常对照外的所有组引起大鼠认知障碍的群体。在第15天测试记忆保留，并在同一天，处死大鼠并分离脑组织以估计乙酰胆碱酯酶（AchE）和脑氧化应激标记物如脂质过氧化物酶（LPO），谷胱甘肽（GSH）（减少））。 ELISA试剂盒用于估计β淀粉样蛋白（Aβ1-42）水平。解剖出大鼠的海马体并研究其组织病理学变化。

[参考文献]

[1]. Lochner M, et al. The muscarinic antagonists Scopolamine and atropine are competitive antagonists at 5-HT3 receptors. Neuropharmacology. 2016 Sep;108:220-8.

[2]. O ET, et al. COGNITIVE-ENHANCING PROPERTIES OF MORINDA LUCIDA (RUBIACEAE) AND PELTOPHORUM PTEROCARPUM (FABACEAE) IN SCOPOLAMINE-INDUCED AMNESIC MICE. Afr J Tradit Complement Altern Med. 2017 Mar 1;14(3):136-141.

[3]. Pattanashetti LA, et al. Evaluation of neuroprotective effect of Quercetin with Donepezil in Scopolamine-induced amnesia in rats. Indian J Pharmacol. 2017 Jan-Feb;49(1):60-64.

[相关活性小分子]

氢溴酸东莨菪碱物理化学性质

[ 沸点 ]:
460.3ºC at 760 mmHg

[ 熔点 ]:
195-199 °C (dry matter)(lit.)

[ 分子式 ]:
C₁₇H₂₂BrNO₄

[ 分子量 ]:
384.265

[ 精确质量 ]:
383.073212

[ PSA ]:
62.30000

[ LogP ]:
1.81410

[ 外观性状 ]:
白色结晶固体粉末

[ 蒸汽压 ]:
2.51E-10mmHg at 25°C

[ 储存条件 ]:
库房低温,通风,干燥

[ 水溶解性 ]:
H2O: 50 mg/mL

氢溴酸东莨菪碱毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YM4550000

CHEMICAL NAME :: 1-alpha-H,5-alpha-H-Tropan-3-alpha-ol, 6-beta,7-beta-epoxy-, (-)-tropate (ester), hydrobromide

CAS REGISTRY NUMBER :: 114-49-8

LAST UPDATED :: 199701

DATA ITEMS CITED :: 21

MOLECULAR FORMULA :: C17-H21-N-O4.Br-H

MOLECULAR WEIGHT :: 384.31

WISWESSER LINE NOTATION :: T C356 A AN DOTJ A1 HOVYR&1Q &EH

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 :: 1270 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3800 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraduodenal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 670 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1880 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 650 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1650 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 203 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 80 mg/kg

TOXIC EFFECTS :: Cardiac - other changes Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 850 mg/kg

TOXIC EFFECTS :: Autonomic Nervous System - parasympatholytic

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 975 mg/kg/13W-I

TOXIC EFFECTS :: Blood - changes in leukocyte (WBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 975 mg/kg/13W-I

TOXIC EFFECTS :: Blood - changes in leukocyte (WBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 300 ug/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 500 ug/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2365 mg/kg

SEX/DURATION :: female 10-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Human HeLa cell

DOSE/DURATION :: 1 pph/5H

REFERENCE :: HUMAA7 Humangenetik. (Heidelberg, Fed. Rep. Ger.) V.1-30, 1964-75. For publisher information, see HUGEDQ. Volume(issue)/page/year: 4,371,1967 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 80511 No. of Facilities: 1011 (estimated) No. of Industries: 3 No. of Occupations: 11 No. of Employees: 7730 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 80511 No. of Facilities: 462 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 19132 (estimated) No. of Female Employees: 16485 (estimated)

氢溴酸东莨菪碱安全信息

[ 危害码 (欧洲) ]:
Xn: Harmful;

[ 风险声明 (欧洲) ]:
R22

[ 安全声明 (欧洲) ]:
S36

[ 危险品运输编码 ]:
UN 1544 6.1/PG 1

[ WGK德国 ]:
3

[ RTECS号 ]:
YM4550000

氢溴酸东莨菪碱上下游产品

氢溴酸东莨菪碱上游产品

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氢溴酸东莨菪碱制备

东莨菪碱以洋金花为原料提取得到。中国的中药麻醉剂洋金花制剂，源于公元2世纪名医华陀的麻沸散，其有效成分就是东莨菪碱。将洋金花粗粉用 50 ℃ 乙醇渗漉，至渗出液几乎无生物碱为止。渗漉液减压蒸馏回收乙醇，所得浸膏用硫酸提取，提取液加碳酸钠调pH9-10，用氯仿提取，提取液蒸馏回收氯仿得总生物碱，然后进行分离、成盐得本品。对洋金花计总收率0.15%。