溴隐亭_用途_密度_沸点_溴隐亭CAS号【25614-03-3】

该品具有多巴胺受体的兴奋作用。可透过血脑屏障，进入中枢神经内，激动多巴胺受体和抑制催乳素及生长激素分泌作用。临床用于帕金森氏症、肢端肥大症和乳溢症等。

[ 描述 ]:

溴隐亭是一种有效的多巴胺D2/D3受体激动剂,可将多巴胺D2受体与8.05±0.2的pKi结合。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 多巴胺受体

信号通路 >> 神经信号通路 >> 多巴胺受体

研究领域 >> 神经疾病

[ 靶点 ]

pKi: 8.05±0.2 (dopamine D2 receptor)[1]

[体外研究]

溴隐亭刺激pEC50为8.15±0.05的CHO细胞中表达的D2多巴胺受体[35S]-GTPγS结合[1]。溴隐亭也是脑一氧化氮合酶的强抑制剂。麦角生物碱溴隐亭(BKT)被发现是纯化神经型一氧化氮合酶(NOS)的强抑制剂(IC50=10±2μM),而它对诱导巨噬细胞NOS(IC50>100μM)的活性较差[2]。溴隐亭被发现可以抑制至少一种人类细胞色素P450酶的活性。溴隐亭是CYP3A4的有效抑制剂,其相互作用的IC50值为1.69μM[3]。

[体内研究]

与对照组相比,溴隐亭(多巴胺激动剂)治疗组(2 mg/kg,i.p.)显示出显著的抗静止作用。当溴隐亭在最后一次7天MPE治疗30分钟后给药并接受FST时,与单独MPE治疗相比,该多巴胺能激动剂产生了显著的剂量依赖性增强MPE抗静止作用(200 mg/kg,p.o.)。溴隐亭(多巴胺激动剂)治疗组(2 mg/kg,i.p.)与对照组相比,不动时间显著减少。与单独使用MPE治疗相比,使用MPE(100和200 mg/kg,p.o.)预处理7天后服用溴隐亭显示出MPE抗静止作用的显著和剂量依赖性增强[4]。与假手术组相比,腹腔内注射溴隐亭可使CCI-IoN组的疼痛评分显著降低,且呈剂量依赖性(0.1 mg和1 mg/Kg),且持续6小时。最高剂量的溴隐亭导致最高评分降低(P<0.01)。作为阳性对照,使用SKF8129(DR1激动剂)。与假手术(注射生理盐水)相比,腹腔内给药导致SMA评分无显著增加。与假手术(注射生理盐水)相比,脑池内注射溴隐亭可显著降低SMA评分。溴隐亭作用持续20分钟。腹腔注射溴隐亭可导致CCI IoN？+？的SMA评分显著降低,且呈剂量依赖性？6-OHDA损伤组与假手术组比较。其作用持续6小时。服用SKF81297可增加痛觉超敏评分。与假手术组(生理盐水注射大鼠)相比,脑池内注射溴隐亭可显著降低SMA评分,其作用持续30分钟[5]。

[激酶实验]

进行[35S]-GTPγS结合分析。细胞膜（25±75 ug）在30°C下，在含有0.1 mM二硫苏糖醇（DTT）和1 uM GDP以及体积为0.9 mL的药物的缓冲液B中培养30分钟。当添加[35S]-GTPγS（50±150 pM，最终浓度）（在100 uL缓冲液B中）以启动反应时，该预培养确保受试激动剂处于平衡状态。除非另有说明，否则将分析混合物再培养20分钟。通过快速过滤和结合放射性测定终止分析，如上述放射性配体结合分析所述。[35S]-GTPγS的总结合量小于添加量的20%[1]。

[动物实验]

小鼠[4]选用瑞士小鼠（20-25克），雌雄各半（共150只）。甲磺酸溴隐亭被用作多巴胺受体（D2）激动剂。氟哌啶醇用蒸馏水稀释，蒸馏水用于注射载体。甲磺酸溴隐亭溶于一滴冰醋酸中，并在蒸馏水中定容。Imipramine溶于0.9%生理盐水中。在强迫游泳试验（FST）和尾部悬吊试验（TST）中，给小鼠组服用氟哌啶醇（0.1 mg/kg，i.p.）和甲磺酸溴隐亭（2 mg/kg，i.p.），持续7天。阳性对照组给予伊米帕明（10 mg/kg，p.o.）作为标准，持续7天。大鼠[5]使用成年雄性Sprague-Dawley大鼠（N=112275-325 g）。6-OHDA注射两周后，使用面罩用2%氟烷对动物进行短暂麻醉（<3分钟），并接受池内给药溴隐亭（7μg/kg溶于5μL溶媒中）或单独给药溶媒（5μL 0.9%生理盐水）。对于腹腔注射，我们使用溴隐亭（1 mg/kg）和SKF81297（3 mg/kg溶于0.9%生理盐水）浓度。恢复期（<2分钟）后，将大鼠置于观察区，由一名盲实验人员进行40分钟的周期测试。

[参考文献]

[1]. Gardner B, et al. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.

[2]. Renodon A, et al. Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.FEBS Lett. 1997 Apr 7;406(1-2):33-6.

[3]. Wynalda MA, et al. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4.

[4]. Rana DG, et al. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014 Jan;35(1):90-7.

[5]. Dieb W, et al. Nigrostriatal dopaminergic depletion increases static orofacial allodynia. J Headache Pain. 2016;17:11.

[ 密度 ]:
1.52 g/cm3

[ 沸点 ]:
891.3ºC at 760 mmHg

[ 分子式 ]:
C₃₂H₄₀BrN₅O₅

[ 分子量 ]:
654.59400

[ 闪点 ]:
492.8ºC

[ 精确质量 ]:
653.22100

[ PSA ]:
118.21000

[ LogP ]:
3.39740

[ 外观性状 ]:
白色结晶粉末

[ 蒸汽压 ]:
4.15E-34mmHg at 25°C

[ 折射率 ]:
1.696

[ 储存条件 ]:
库房通风干燥低温

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KE7625000

CHEMICAL NAME :: Ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpr opyl)-, (5'-alpha)-

CAS REGISTRY NUMBER :: 25614-03-3

LAST UPDATED :: 199703

DATA ITEMS CITED :: 38

MOLECULAR FORMULA :: C32-H40-Br-N5-O5

MOLECULAR WEIGHT :: 654.68

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 6 mg/kg/60D-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 72 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 :: >800 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 :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 200 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 - rabbit

DOSE/DURATION :: >1 gm/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 - rabbit

DOSE/DURATION :: 12 mg/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 7 gm/kg/2Y-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2423 ug/kg

SEX/DURATION :: lactating female 3 week(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 ug/kg

SEX/DURATION :: lactating female 9 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - postpartum

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 ug/kg

SEX/DURATION :: lactating female 15 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - postpartum

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1750 ug/kg

SEX/DURATION :: lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - postpartum

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 21700 ug/kg

SEX/DURATION :: female 28 week(s) pre-mating female 1-21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 3500 ug/kg

SEX/DURATION :: female 14 day(s) pre-mating female 1-21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 11900 ug/kg

SEX/DURATION :: female 77 day(s) pre-mating female 1-42 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 11200 ug/kg

SEX/DURATION :: female 44 day(s) pre-mating female 1-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2800 ug/kg

SEX/DURATION :: female 24-52 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 70 mg/kg

SEX/DURATION :: female 13-19 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 1950 ug/kg

SEX/DURATION :: female 5-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 5100 ug/kg

SEX/DURATION :: lactating female 3 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - postpartum

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 17500 ug/kg

SEX/DURATION :: male 35 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 88 mg/kg

SEX/DURATION :: female 1-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 8125 ug/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 84 mg/kg

SEX/DURATION :: lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 200 mg/kg

SEX/DURATION :: female 50 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 212 mg/kg

SEX/DURATION :: female 32 day(s) pre-mating female 21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 4 mg/kg

SEX/DURATION :: male 10 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 750 ug/kg

SEX/DURATION :: female 43-48 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 600 ug/kg

SEX/DURATION :: female 42-47 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 8 mg/kg

SEX/DURATION :: female 27-30 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 400 ug/kg

SEX/DURATION :: male 50 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 3 mg/kg

SEX/DURATION :: male 84 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 75200 ug/kg

SEX/DURATION :: female 42-49 week(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition Reproductive - Maternal Effects - postpartum

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 22400 ug/kg

SEX/DURATION :: female 42-44 week(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Endocrine - estrogenic

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 1 mg/kg

SEX/DURATION :: female 23 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

MUTATION DATA

TEST SYSTEM :: Rodent - rat

DOSE/DURATION :: 4 mg/kg

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 36,2223,1976 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6252 No. of Facilities: 9 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 339 (estimated) No. of Female Employees: 170 (estimated)

[ 危害码 (欧洲) ]:
Xn,Xi

[ 风险声明 (欧洲) ]:
R20/21/22:Harmful by inhalation, in contact with skin and if swallowed .

[ 安全声明 (欧洲) ]:
S45

详细合成路线

溴隐亭上游产品

溴隐亭下游产品

由麦角隐亭和N-溴丁二酸亚胺反应得到。

公司名：上海源溪生物科技有限公司

区域：上海市浦东新区

价格：
￥需询单/1g

联系人：赖经理

产品详情：Bromocriptine

公司名：上海阿拉丁生化科技股份有限公司

区域：上海市浦东新区

价格：
￥3655.0/1g ￥339.0/100mg ￥需询单/1g ￥需询单/1g

联系人：阿拉丁李高志

产品详情：溴隐亭

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