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::: Pramipexole dihydrochloride 普拉克索 :::


帕金森病是一种常见的神经内科疾病, 在老年人中为常见疾病,在60岁以上病人的发病率为1%。目前市场上主要的抗帕金森氏病的药物有:
(1)左旋多巴, 最经典的治疗帕金森氏病的药物
但是由于左旋多巴不容易穿过血脑屏障, 患者通常需要服用大剂量引起如呕吐与不自主运动的严重副作用。
(2)多巴胺受体激动剂
早期的多巴胺受体激动剂有溴隐停、培高利特等药物, 为非选择性多巴胺受体激动剂, 作用效果较弱, 不能单独使用作为帕金森氏病的治疗方法;长期临床应用证实DA激动剂中非麦角类远远优于麦角类衍生物,因为前者作用具有选择性。新型的非麦角类衍生物是目前研究的热点,有卡麦角林、Ropinirole、Pramipexole等。而且Pramipexole治疗帕金森的机理为其刺激多巴胺受体,它高度选择性地作用于DA-2(多巴胺受体2亚型)产生,而其他多巴胺受体激动剂为DA-2部分激动剂。

Pramipexole由德国Boehringer Ingelheim公司开发,在1997年5月10日FDA批准Pramipexole上市,商品名Mirapex。在美国由 Boehringer Ingelheim 公司与 Pharmacia 公司共同售卖,它是FDA在过去6年中首次批准用于帕金森的药物。MIRAPEX Tablets contain pramipexole, a dopamine agonist indicated for the treatment of the signs and symptoms of idiopathic Parkinson’s disease. The chemical name of pramipexole dihydrochloride is (S)-2-amino- 4, 5, 6, 7-tetra-hydro-6-(propylamino) benzothiazole dihydrochloride mono-hydrate. Its empirical formula is C10H17N3S · 2 HCl · H2O, and its molecular weight is 302.27.

Pramipexole dihydrochloride is a white to off- white powder substance. Melting occurs in the range of 296 ~ 301°C, with decomposition. Pramipexole dihydrochloride is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane.

Pramipexole是非麦角类衍生物, 它的主要优点为:Pramipexole高度选择性地作用于DA-2受体;早期可以单独使用治疗帕金森氏病, 晚期可与多巴胺合用治疗帕金森氏病, 国外同时对于Pramipexole用于治疗RLS症(restless leg syndrome)进行研究, 认为是有效的, 而且Pramipexole对多巴胺的神经有保护作用, 神经保护和RLS症的治疗是其独一无二的优点, 可大大延缓病情的发展, 保证了患者的健康。口服后, Pramipexole迅速吸收, 2小时内达到峰值浓度, 绝对生物利用度大约为90%。在老年人中消除半衰期为12小时, 90%的药物以原型药物分泌, 主要通过尿液排泄。

非麦角类衍生物是目前帕金森氏病研究的热点, 有着广阔的应用前景。Pramipexole因为其作用选择性, 且能够单独用于帕金森氏病, 将来极可能成为帕金森氏病的首选药。

Pramipexole and HCL salts
Product name:
Pramipexole dihydrochloride monohydrate, Pramipexole 2HCL, Pramipexole
Cas Number:
191217-81-9, 104632-25-9, 104632-26-0
Chemical name:
(S)-2-Amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate
synonym: (6S)-2-Amino-6-propyltetrahydrobenzothiazole dihydrochloride monohydrate
Other form:
(S)-2-Amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole and it's dihydrochloride.

PRAMIPEXOLE

Appearance: White crystalline powder Specificat rotation [a] 20/D: -65 ~ -68 degrees
Loss on drying: not more than 0.5% Heavy metal: not more than 20ppm
Residue on ignition: not more than 0.5% Assay: not less than 98.5%
single impurity: not more than 0.5% Total impurities: not more than 1.0%

Intermediates for Pramipexole
1. (6S)-2-Amino-6-propionamidotetrahydrobenzothiazole
Cas Number:
106006-84-2

2. (6S)-2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole
Cas Number:
106092-09-5

Appearance: White crystalline powder Specificat rotation [a] 20/D: -87 ~ -91 degrees
Loss on drying: not more than 0.5% Heavy metal: not more than 20ppm
Residue on ignition: not more than 0.5% Assay: not less than 98.0%

3. (+/-)-2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole
Cas Number:
106006-83-1

 

 
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