中文名称:

马来酸替加色罗

中文同义词:

马来酸替加色罗;2-[(5-甲氧基-1H-吲哚-3-基)亚甲基]-N-戊基卡巴肼马来酸盐;马来酸替加色罗杂质

英文名称:

Tegaserod maleate

英文同义词:

SDZ-HTF-919;TEGASEROD MALEATE;ZELMAC;2-[(5-METHOXY-1H-INDOL-3-YL)METHYLENE]-N-PENTYLHYDRAZINECARBOXIMIDAMIDE, MALEATE;2-[(5-methoxy-1h-indole-3-yl)methylene]-n-pentylcarbazimidamide hydrogen maleate;TegaserodMalate;TegastrodMaleate;SDZ-HTF-919, Zelmac, 2-[(5-Methoxy-1H-indol-3-yl)methylene]-N-pentylhydrazinecarboximidamide, Maleate

CAS号:

189188-57-6

分子式:

C20H27N5O5

分子量:

417.46

EINECS号:

630-469-2

相关类别:

医药原料;小分子抑制剂;原料药;医药 吲哚类选择性5-HT4受体部分激动剂;医药原料药-科研原料;医药原料药;原料;Chiral Compound;Intermediates Fine Chemicals;Active Pharmaceutical Ingredients;Pharmaceuticals;Tegaserod

Mol文件:

189188-57-6.mol

熔点 

180-183°C

储存条件 

2-8°C

形态

powder

颜色

white to beige

CAS 数据库

189188-57-6(CAS DataBase Reference)

应用

马来酸替加色罗在临床应用主要是：首先，对IBS 及功能性便秘的治疗作用。马来酸替加色罗是第一个应用于治疗C -IBS 的5 -HT4受体部分激动剂。

药理作用

本品是5-HT受体的部分激动剂，与5–HT4受体能紧密结合，体现高亲和力；与5-HT1受体有中度亲和力，而对5–HT3受体则不能结合，体现无亲和力。本品激活5-HT4受体可触发其他神经递质如降钙素相关基因肽的释放，刺激肠蠕动反射及肠道腺体分泌，并抑制内脏的敏感性。

毒理研究

在实验中，动物所用药物剂量远远高出了人体临床治疗所推荐剂量。从运用该药及其在人体内形成的主要代谢物对兔离体心脏复极影响的实验中发现，药物浓度为0.5 μM 时，Q -T 变化小于5 %；当浓度为50μM(人约为人体临床口服推荐剂量所产生血药浓度的500 ～1000 倍)时，Q-T 变化为1.4 %。在大鼠、小鼠和狗体中进行的高剂量胃肠道影响实验中，发现马来酸替加色罗对相应的靶器官无毒性；该蓟也不影响免疫系统和生殖能力；在大鼠和小鼠上进行的致癌实验表明该药也不存在致癌能力，体内与体外实验表明不存在致突变能力，也未使DNA 损害。

生物活性

Tegaserod maleate 是选择性的、5-HT4 受体的部分激动剂和 5-HT2B 受体的拮抗剂。Tegaserod maleate 在胃肠道中表现出促进的作用。

靶点

Target Value 5-HT4 receptor ()

Target

Value

5-HT4 receptor ()

体外研究

Tegaserod was metabolized in human liver microsomes to O-desmethyl tegaserod at a low rate. Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pK i =7.5, 8.4 and 7.0, respectively). Tegaserod (0.1-3 μM) inhibits 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA 2 =8.3), consistent with 5-HT2B receptor antagonist activity.

体内研究

Tegaserod increases the amplitude of excitatory postsynaptic currents mediated by nicotinic acetylcholine receptors which may contribute to the prokinetic effects by facilitating excitatory neurotransmission in mice. Tegaserod (0.1 mg/kg) significantly accelerates the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. Tegaserod (5, 10, 50, 100 μg/mL) promotes hindlimb motor function at 6 weeks after spinal cord injury compared to the control group receiving vehicle only. Animal Model: Female C57BLKS/J db/db mice. Dosage: 0.1, 0.5, 1.0, 2.0 mg/kg. Administration: IP 15 min prior to gastric loading. Result: Produced a dramatic decrease in the fraction of the meal remaining in the stomach for doses as low as 0.1 mg/kg (0.1 mg/kg). Accelerated gastric emptying, with a reduction of nearly 80% in the fraction remaining at 30 min (P < 0.0001) (0.1 mg/kg). Induced a significant decrease in the gastric emptying rate as the amount of the meal remaining at 30 min was significantly greater (2.0 mg/kg). Resulted in inhibition of tegaserod-induced increased gastric emptying (0.1 mg/kg). Animal Model: Three- to four-month-old female C57BL/6J mice. Dosage: 5, 10, 50, 100 μg/mL. Administration: Alzet pumps into non-injured spinal cords. Result: Showed a less intense astrogliosis within and in the vicinity of the compression lesion site when compared to vehicle-only-treated mice. Showed a smaller lesion area when compared to vehicle-onlytreated mice. Showed a higher staining intensity of 5-HT-immunoreactive axons 1 mm rostral, but not caudal to the lesion center as determined in cross-sections and quantification by ImageJ analysis.

Animal Model:

Female C57BLKS/J db/db mice.

Dosage:

0.1, 0.5, 1.0, 2.0 mg/kg.

Administration:

IP 15 min prior to gastric loading.

Result:

Produced a dramatic decrease in the fraction of the meal remaining in the stomach for doses as low as 0.1 mg/kg (0.1 mg/kg). Accelerated gastric emptying, with a reduction of nearly 80% in the fraction remaining at 30 min (P < 0.0001) (0.1 mg/kg). Induced a significant decrease in the gastric emptying rate as the amount of the meal remaining at 30 min was significantly greater (2.0 mg/kg). Resulted in inhibition of tegaserod-induced increased gastric emptying (0.1 mg/kg).

Animal Model:

Three- to four-month-old female C57BL/6J mice.

Dosage:

5, 10, 50, 100 μg/mL.

Administration:

Alzet pumps into non-injured spinal cords.

Result:

Showed a less intense astrogliosis within and in the vicinity of the compression lesion site when compared to vehicle-only-treated mice. Showed a smaller lesion area when compared to vehicle-onlytreated mice. Showed a higher staining intensity of 5-HT-immunoreactive axons 1 mm rostral, but not caudal to the lesion center as determined in cross-sections and quantification by ImageJ analysis.

化学性质 

类白色结晶粉末。