尼麦角林

中文名称:

尼麦角林

中文同义词:

5-溴烟酸 10-甲氧基-1,6-二甲基麦角灵-8-甲酯;麥角溴菸鹼酯;麦角灵;麦角溴烟酯;脑通;你先获宁;10-甲氧基-1,6-二甲基麦角林-8-甲醇 5-溴烟酸酯;尼麦角林

英文名称:

Nicergoline

英文同义词:

nicergoline Fr.P;10-Methoxy-1,6-dimethylergoline-8β-methanol 5-bromonicotinate;Ergoline-8-methanol, 10-methoxy-1,6-dimethyl-, 5-bromo-3-pyridinecarboxylate (ester), (8.beta.)-;1,6-Dimethyl-8b-(5-bromonicotinoyloxymethyl)-10a-methoxyergoline;Cergodum;Circo-Maren;Dilasenil;Duracebrol

CAS号:

27848-84-6

分子式:

C24H26BrN3O3

分子量:

484.39

EINECS号:

248-694-6

相关类别:

化工原料;医药原料药-科研原料;中药对照品;小分子抑制剂;原料药;吡咯;Miscellaneous Natural Products;Miscellaneous;Adrenoceptor;SPIROPITAN;标准品;医用原料;脑血管用药;医药原料药;沃德森定制目录1;杂质世界-钆布醇;脑部用药

Mol文件:

27848-84-6.mol

 

 

熔点 

136-138°

沸点 

594.4±50.0 °C(Predicted)

密度 

1.3558 (rough estimate)

折射率 

1.6200 (estimate)

储存条件 

2-8°C

溶解度 

Practically insoluble in water, freely soluble in methylene chloride, soluble in ethanol (96 per cent).

形态

neat

酸度系数(pKa)

6.33±0.40(Predicted)

水溶解性 

Soluble in alcohol, chloroform, and acetone. Insoluble in water.

Merck 

14,9496

概述

尼麦角林是一种半合成麦角生物碱衍生物。自20世纪60年代研发成功以来，已经在50多个国家注册使用。国内也已被广泛应用于脑血管病、痴呆以及头晕等多种疾患。

作用机制

改善脑循环作用：尼麦角林可以扩张阻力血管，从而改善脑循环。该药物作为特异性肾上腺素α1受体阻滞剂，可抑制阻力血管的加压反射，增加大鼠双侧颈内动脉结扎后再灌注期的局部脑血流量和葡萄糖利用率；降低麻醉犬的血压，但不影响其脑血流量；且能改善家兔实验性蛛网膜下腔出血所诱发的脑血管痉挛。 改善脑代谢及电生理活动：尼麦角林长期治疗，可以提高老龄大鼠脑提取物的葡萄糖利用率。急性用药可使老年受试者的记忆功能改善，脑电地形图总能量增高，慢波减少。

生物活性

Nicergoline，溴烟碱酸的麦角林衍生物，是一种有效，选择性和具有口服活性的 α1A-肾上腺素能受体拮抗剂。Nicergoline 具有血管舒张作用。Nicergoline 可以改善阿尔茨海默症小鼠的认知功能。

靶点

Target Value alpha-1A adrenergic receptor ()

Target

Value

alpha-1A adrenergic receptor ()

 

体外研究

Nicergoline (0.3-30 μM; 24 h) attenuates activated microglia- and astrocytes-induced neuronal cell death. Nicergoline (0.3-30 μM; 48 h) suppresses the production of proinflammatory cytokines and superoxide anion by activated microglia.

体内研究

Nicergoline (10 mg/kg; i.v. once daily for 60 d) improves impaired neurogenesis and cognitive competence in mice with Alzheimers disease. Nicergoline (10 mg/kg; i.v. once daily for 60 d) inhibits apoptosis, inflammation and oxidative stress in hippocampal cells, and regulates the activity of hippocampal cells through the PI3K/AKT signaling pathway in mice. Animal Model: 3×Tg-AD mice (male, 28-35 g, 6 weeks) with the Alzheimers disease Dosage: 10 mg/kg Administration: I.v. once daily for 60 days Result: Improved neurogenesis and cognitive competence. Decreased the degree of dementia. Downregulated pathogenic Aβ-42 and -40 peptides and APP in the hippocampi. Increased Levels of the neuroprotective forkhead box protein P2 (Foxp2), Src homology 2-containing inositol phosphatase (SxIP) and end-binding proteins (EB) in the hippocampi. Exhibited marked differences in the dispersion of the pyramidal cell layer between the nicergoline-treated and control groups.

Animal Model:

3×Tg-AD mice (male, 28-35 g, 6 weeks) with the Alzheimers disease

Dosage:

10 mg/kg

Administration:

I.v. once daily for 60 days

Result:

Improved neurogenesis and cognitive competence. Decreased the degree of dementia. Downregulated pathogenic Aβ-42 and -40 peptides and APP in the hippocampi. Increased Levels of the neuroprotective forkhead box protein P2 (Foxp2), Src homology 2-containing inositol phosphatase (SxIP) and end-binding proteins (EB) in the hippocampi. Exhibited marked differences in the dispersion of the pyramidal cell layer between the nicergoline-treated and control groups.

危险品标志 

Xn

危险类别码 

22

安全说明 

36

危险品运输编号 

1544

WGK Germany 

3

RTECS号

KE6341000

HazardClass 

6.1(b)

PackingGroup 

III

海关编码 

29396100

毒性

LD50 in male mice, rats (mg/kg): 860, 2800 orally; 46, 43 i.v. (Neumann, Lauschner)