甲磺酸溴隐亭

背景作用适应症制备生物活性靶点体外研究体内研究甲磺酸溴隐亭试剂级价格

甲磺酸溴隐亭

CAS号:22260-51-1
英文名:Bromocriptine mesylate
中文名:甲磺酸溴隐亭
CBNumber:CB4335584
分子式:C33H44BrN5O8S
分子量:750.7
MOL File:22260-51-1.mol

甲磺酸溴隐亭化学性质

熔点 :192-196° (dec)
比旋光度 :D20 +95° (c = 1 in methanol-methylene chloride)
储存条件 :2-8°C
溶解度 :H₂O: 0.8 mg/mL
形态 :solid
酸度系数(pKa) :4.90(at 25℃)
颜色 :white
旋光性 (optical activity) :[α]20/D +95°, c = 1 in methanol: methylene chloride (1:1)(lit.)
Merck :13,1400
BRN :4115238
稳定性 :Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months
InChIKey :NOJMTMIRQRDZMT-JGYCFGIMSA-N
CAS 数据库 :22260-51-1(CAS DataBase Reference)

安全信息

危险品标志 :Xn
危险类别码 :20/21/22
安全说明 :22-24/25-36
危险品运输编号 :UN 3077 9 / PGIII
WGK Germany :3
RTECS号 :KE1595000
F :3-10
海关编码 :29396900
毒性 :LD50 in mice, rats, rabbits (mg/kg): 190, 72, 12.5 i.v. (Parkes)

甲磺酸溴隐亭性质、用途与生产工艺

背景甲磺酸溴隐亭最早由诺华公司开发，主要用于抗震颤麻痹，抑制生理性泌乳和治疗催乳激素过高引起的经前期综合征、肢端肥大症、女性不育症和亨丁顿舞蹈病。临床用于治疗帕金森病，与催乳素有关的生殖系统功能异常，如闭经、溢乳症、经前综合征、产褥期乳腺炎、纤维囊性乳腺瘤、男性阳痿或性欲减退，还可用于垂体腺瘤等。甲磺酸溴隐亭快速释放的口服制剂辅助用于Ⅱ型糖尿病的治疗，该药2009年5月获得ＦＤＡ批准。
作用本品又称溴麦亭、溴化麦角隐亭、溴克丁、麦角克碱、麦角环肽、抑乳停、甲磺酸溴隐亭，是麦角生物碱的半合成衍生物，能特异地兴奋中枢多巴胺受体，对其他受体有拮抗作用。无麦角类的收缩子宫和血管作用。可抑制PRL、LH的分泌，激活脑内新纹状体的多巴胺受体，控制震颤麻痹综合征；通过中枢或外周的作用松弛血管平滑肌，减低交感神经兴奋性，进而使血压下降，脉率不增加。
适应症适用于治疗高泌乳素血症及泌乳素瘤，或作为泌乳素瘤的术前准备或术后治疗；亦用于治疗垂体生长激素瘤、巨人症及肢端肥大症；或用于垂体促皮质素瘤及库欣(Cushing)病合并血糖升高者的治疗。可用于治疗多囊卵巢综合征，对排卵功能障碍性不孕症有效。对乳腺增生、回乳、月经紊乱、经前紧张综合征、肝性脑病、糖尿病、特发性水肿、垂体性甲亢及甲状腺功能减退症均有一定效果。
制备

1）溴隐亭的合成

将α-麦角隐亭12g（20.8mmoL）和二氯甲烷120mL加入反应瓶中，搅拌溶清后依次加入5，5-二溴巴比妥酸3.69g（12.9mmoL）、33％氢溴酸的冰乙酸溶液0.2mL，控温25～30℃反应5～6h，过滤，滤液依次用1moL／L的硫代硫酸钠（30mL），5％的碳酸氢钠溶液（30mL），20％氯化钠溶液（30mL）洗涤。有机相用无水硫酸镁干燥，过滤，并加入硅胶36g浓缩将溶剂完全拉干。柱层析：流动相先为二氯甲烷，后为V（二氯甲烷）∶V（丙酮）＝6∶1的混合溶液。得10.6g溴隐亭，收率７8％。

2）甲磺酸溴隐亭的合成

将溴隐亭6.0g用二氯甲烷120mL溶清后加入2-丁酮200mL，控制内温20～30℃，加入甲磺酸1.14g，生成结晶型沉淀，搅拌1h。滤出固体，用2-丁酮30mL洗涤，干燥得6.13g甲磺酸溴隐亭，收率86％。
生物活性 Bromocriptine mesylate 是一种有效的多巴胺 D2/D3 受体激动剂，结合多巴胺 D2 受体，pKi 为 8.05±0.2。
靶点

pKi: 8.05±0.2 (dopamine D2 receptor)
体外研究

Bromocriptine stimulates [ ³⁵ S]-GTPγS binding at D2 dopamine receptor expressed in CHO cells with pEC ₅₀ of 8.15±0.05. Bromocriptine also is a strong inhibitor of brain nitric oxide synthase. The ergot alkaloid Bromocriptine (BKT) is found to act as a strong inhibitor of purified neuronal nitric oxide synthase (NOS) (IC ₅₀ =10±2 μM) whereas it is poorly active towards inducible macrophage NOS (IC ₅₀ >100 μM) . Bromocriptine is found to inhibit the activity of at least one human cytochrome P450 enzyme. Bromocriptine is a potent inhibitor of CYP3A4 with a calculated IC ₅₀ value for the interaction of 1.69 μM.
体内研究

Bromocriptine mesylate (2 mg/kg, i.p.) is administered for 7 days in groups of mice in forced swimming test (FST) and tail suspension test (TST). Bromocriptine group shows significant anti-immobility action as compared to control. When Bromocriptine administered 30 min after the last dose of 7 days MPE treatment and subjected to FST, this dopaminergic agonist produces significant and dose dependent potentiation of anti-immobility action of MPE (200 mg/kg, p.o.) as compared to MPE treatment alone. Bromocriptine treatment group shows a significant reduction of immobility time as compared to control. Bromocriptine administration after 7 days pretreatment with MPE (100 and 200 mg/kg, p.o.) shows significant and dose dependent potentiation of anti-immobility action of MPE as compared to MPE treatment alone. Intracisternal administration of Bromocriptine decreases significantly the static mechanical allodynia (SMA) score compared to that of sham (saline-injected rats) and its effect lasted for 30 min. Intraperitoneal administration of Bromocriptine induces a significant, dose dependent (0.1 mg and 1 mg/kg) decrease in pain scores in CCI-IoN group when compared to sham and its effect lasted for 6 h. The highest dose induces the highest score decrease (P<0.01). Bromocriptine effect lasts for 20 min. Intraperitoneal administration of Bromocriptine induces a significant dose dependent decrease in SMA score in CCI-IoN+6-OHDA lesioned group compared to that of sham. Its effect lasts for 6 h.
类别有毒物质
毒性分级中毒
急性毒性口服-小鼠 LD50: 2502 毫克/公斤; 静脉-大鼠 LD50: 10.5 毫克/公斤
可燃性危险特性热分解排出有毒氮氧化物,硫氧化物和溴化物烟雾
储运特性库房通风干燥低温
灭火剂水,干粉,二氧化碳,泡沫,沙土