1-(2-溴异戊酰)脲

Bromisoval(BU)具有抗炎作用,一直以来被用作镇静剂和催眠药。

信号通路 >> 其他 >> 其他

研究领域 >> 炎症/免疫

研究领域 >> 神经疾病

Bromisoval(BU)抑制一氧化氮(NO)释放和促炎细胞因子在脂多糖(LPS)-β2细胞(一种小鼠小胶质细胞系)中的表达。 Bromisoval抑制LPS诱导的信号转导和转录激活因子1(STAT1)的磷酸化和干扰素调节因子1(IRF1)的表达。 Janus激酶1(JAK1)抑制剂filgotinib比Bromisoval抑制NO释放更弱,尽管filgotinib几乎完全阻止LPS诱导STAT1磷酸化。敲除JAK1,STAT1或IRF1不会影响Bromisoval对LPS诱导NO的抑制作用。 Bromisoval和filgotinib的组合协同抑制NO释放。线粒体复合物I抑制剂鱼藤酮,其不阻止STAT1磷酸化或IRF1表达,抑制促炎介质表达不如Bromisoval显着。 Bromisoval和鱼藤酮以相似的程度降低细胞内ATP(iATP)水平。鱼藤酮和filgotinib的组合抑制LPS处理的BV2细胞中的NO释放与Bromisoval一样强[1]。

Bromisoval(Bromvaletone)和carbromal是每个系列中最有效的中枢抑制剂。腹腔注射Bromisoval后雄性小鼠的抑郁活性(ISD50值)和急性毒性(LD50值)分别为0.35(0.30-0.39)和3.25(2.89-3.62)mmol/kg [2]。

从BV2细胞培养物获得调理培养基，所述BV2细胞培养物已经在含有1μg/ ml LPS，含有或不含有Bromisoval（BU）（1-100μg/ mL）或其他试剂的E2培养基中孵育24小时，并进行NO测定。为了通过细胞蛋白质含量使释放的NO水平正常化，用RIPA缓冲液（50mM Tris-HCl，pH 8.0,150mM氯化钠，0.5％w / v脱氧胆酸钠，0.1％w / v十二烷基硫酸钠， 1.0％w / v NP-40替代品）和蛋白质含量由BCA蛋白质测定试剂测定[1]。

使用鼠小胶质细胞系BV2。将BV2细胞维持在补充有10％胎牛血清的培养基中。将BV2细胞接种在4孔培养板中的孔上，并与LPS孵育30分钟至24小时。当研究Bromisoval（BU）或其他药物的作用时，将BV2细胞与适当的药剂（例如Bromisoval）一起孵育30分钟，然后加入LPS [1]。

将化合物（包括Bromisoval）在0.5％羧甲基纤维素水溶液中的悬浮液腹膜内给予体重25-35g的成年雄性白化小鼠。所有测试均在10只小鼠的组中进行[2]。

[1]. Kawasaki S, et al. Effects of hypnotic bromovalerylurea on microglial BV2 cells. J Pharmacol Sci. 2017 Jun;134(2):116-123.

[2]. Mrongovius RI, et al. Comparison of the bromureide sedative-hypnotic drugs, bromvaletone (bromisoval) and carbromal, and their chloro analogues in mice. Clin Exp Pharmacol Physiol. 1976 Sep-Oct;3(5):443-7.

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DATA ITEMS CITED :

10

MOLECULAR FORMULA :

C6-H11-Br-N2-O2

MOLECULAR WEIGHT :

223.10

WISWESSER LINE NOTATION :

ZVMVYEY1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Behavioral - coma Gastrointestinal - nausea or vomiting

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 1,1238,1955

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

57 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 7,513,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1 gm/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 7,262,1948

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1340 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1213,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

660 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1213,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

450 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,738,1982

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1289,1935

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Rectal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1400 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TOIZAG Toho Igakkai Zasshi. Journal of Medical Society of Toho University. (Toho Daigaku Igakkai, 21-16, Omori-nishi, 5-chome, Ota-ku, Tokyo 143, Japan) V.1- 1954- Volume(issue)/page/year: 7,513,1960

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Amphibian - frog

DOSE/DURATION :

900 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1289,1935