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氟吗西尼

氟吗西尼用途

Flumazenil 是一种有竞争性的 GABAA receptor 拮抗剂,用于治疗苯二氮类药物过量问题。

氟吗西尼名称

[ CAS 号 ]:
78755-81-4

[ 中文名 ]:
氟马西尼

[ 英文名 ]:
Flumazenil

[中文别名 ]:

[英文别名 ]:

Romazicon
Lanexat
Anexate
Ro-15-1788
Ro 15-1788
YM-684
Ro 1722
Mazicon
Flumazenil
FMZ

氟吗西尼生物活性

[ 描述 ]:

Flumazenil 是一种有竞争性的 GABAA receptor 拮抗剂,用于治疗苯二氮类药物过量问题。

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> GABA受体

信号通路 >> 神经信号通路 >> GABA受体

研究领域 >> 神经疾病

[体内研究]

氟马西尼与中枢苯二氮卓受体相互作用,以拮抗或逆转苯二氮卓类激动剂和反向激动剂的行为,神经和电生理作用。氟马西尼在肝性脑病中有一定的益处,但在进行精心设计的临床试验之前,必须将肝性脑病视为氟马西尼的研究指征。氟马西尼已经被证明可以逆转单独使用苯二氮卓类药物或苯二氮卓类药物与其他药物联合使用引起的镇静作用,但是当怀疑使用环状抗抑郁药时,不应该使用它[1]。氟马西尼(1 mg/kg)在升高的迷宫和光/暗试验中测试的BALB/c小鼠中诱导强烈的抗焦虑作用[2]。氟马西尼(10 mg/kg)可有效预防大鼠中allopregnanolone的减少[3]。氟马西尼(5-20mg/kg)拮抗地西泮的抗惊厥和不良反应,但不影响小鼠的GYKI 52466。氟马西尼在MES模型中略微降低了NBQX的抗惊厥活性,但在PTZ试验中没有[4]。氟马西尼(3.0 mg/kg)可阻止慢性乙醇治疗的退出,从而减少开放臂时间和开放臂进入百分比[5]。

[动物实验]

在实验测试前20分钟腹腔注射氟马西尼，体积为10mL / kg体重。用树脂玻璃覆盖的两个聚氯乙烯盒（20×20×14cm）通过不透明的塑料通道（5×7×10cm）连接。其中一个盒子变暗了。 100瓦的台灯在另一个箱子上方40厘米处的灯光提供了唯一的室内照明。选择该光水平（300勒克斯）是为了避免在对照动物的点亮盒中（时间焦虑行为的测量）中及时检测到应变差异。实际上，在先前的实验中，BALB / c小鼠仅在高光条件下与C57BL / 6不同。受试者在1400至1700小时之间的5分钟内进行单独测试。将小鼠放在点亮的盒子中以开始测试。在隧道中的第一个条目之后记录在点亮的框中花费的时间以及从暗盒到点亮的盒子的过渡的数量。

[参考文献]

[1]. Hoffman EJ, et al. Flumazenil: a benzodiazepine antagonist. Clin Pharm. 1993 Sep;12(9):641-56; quiz 699-701.

[2]. Belzung C, et al. Flumazenil induces benzodiazepine partial agonist-like effects in BALB/c but not C57BL/6 mice. Psychopharmacology (Berl). 2000 Jan;148(1):24-32.

[3]. Fernandez-Guasti A, et al. Flumazenil blocks the anxiolytic action of allopregnanolone. Eur J Pharmacol. 1995 Jul 25;281(1):113-5.

[4]. Loscher W, et al. Effects of the non-NMDA antagonists NBQX and the 2,3-benzodiazepine GYKI 52466 on different seizure types in mice: comparison with diazepam and interactions with flumazenil. Br J Pharmacol. 1994 Dec;113(4):1349-57.

[5]. Moy SS, et al. Flumazenil blockade of anxiety following ethanol withdrawal in rats. Psychopharmacology (Berl). 1997 Jun;131(4):354-60.

[相关活性小分子]

氟吗西尼物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
528.0±50.0 °C at 760 mmHg

[ 熔点 ]:
201-203°C

[ 分子式 ]:
C₁₅H₁₄FN₃O₃

[ 分子量 ]:
303.288

[ 闪点 ]:
273.1±30.1 °C

[ 精确质量 ]:
303.101929

[ PSA ]:
64.43000

[ LogP ]:
0.67

[ 外观性状 ]:
solid | white

[ 蒸汽压 ]:
0.0±1.4 mmHg at 25°C

[ 折射率 ]:
1.634

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
128 mg/L

氟吗西尼毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NI2922170

CHEMICAL NAME :: 4H-Imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylic acid, 8-fluoro-5,6-dihydro-5-methyl-6- oxo-, ethyl ester

CAS REGISTRY NUMBER :: 78755-81-4

LAST UPDATED :: 199612

DATA ITEMS CITED :: 15

MOLECULAR FORMULA :: C15-H14-F-N3-O3

MOLECULAR WEIGHT :: 303.32

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 5700 ng/kg/C

TOXIC EFFECTS :: Cardiac - cardiomyopathy including infarction Cardiac - arrhythmias (including changes in conduction) Cardiac - change in rate

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 304,1415,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 2 mg/kg/2D-I

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - excitement Behavioral - aggression

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 339,488,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 4 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Cardiac - EKG changes not diagnostic of specified effects Cardiac - pulse rate increase, without fall in BP

REFERENCE :: PECAE5 Pediatric Emergency Care. (Williams & Wilkins, 428 E. Preston St., Baltimore, MD 21202) V.1- 1985- Volume(issue)/page/year: 11,186,1995

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4200 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - tremor Behavioral - rigidity (including catalepsy)

REFERENCE :: JTCEEM Journal de Toxicologie Clinique et Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.5- 1985- Volume(issue)/page/year: 7,223,1987

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1360 mg/kg

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

REFERENCE :: DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,402,1982

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 85 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - rigidity (including catalepsy)

REFERENCE :: JTCEEM Journal de Toxicologie Clinique et Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.5- 1985- Volume(issue)/page/year: 7,223,1987

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1300 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - tremor Behavioral - rigidity (including catalepsy)

REFERENCE :: JTCEEM Journal de Toxicologie Clinique et Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.5- 1985- Volume(issue)/page/year: 7,223,1987

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 4 gm/kg

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

REFERENCE :: DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,402,1982

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1 gm/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,201,1992

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 143 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - rigidity (including catalepsy)

REFERENCE :: JTCEEM Journal de Toxicologie Clinique et Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.5- 1985- Volume(issue)/page/year: 7,223,1987

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >640 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,201,1992

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >30 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,201,1992

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 2 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - tremor Behavioral - rigidity (including catalepsy)

REFERENCE :: JTCEEM Journal de Toxicologie Clinique et Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.5- 1985- Volume(issue)/page/year: 7,223,1987 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 21 mg/kg

SEX/DURATION :: female 14-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - behavioral

REFERENCE :: PNPPD7 Progress in Neuro-Psychopharmacology and Biological Psychiatry. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.6- 1982- Volume(issue)/page/year: 17,151,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 220 mg/kg

SEX/DURATION :: female 11-21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - behavioral

REFERENCE :: GEPHDP General Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.6- 1975- Volume(issue)/page/year: 22,43,1991

氟吗西尼安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危害码 (欧洲) ]:
Xi

[ 风险声明 (欧洲) ]:
R36/37/38:Irritating to eyes, respiratory system and skin .

[ 安全声明 (欧洲) ]:
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice . S27:Take off immediately all contaminated clothing . S36/37/39:Wear suitable protective clothing, gloves and eye/face protection .

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
2

[ RTECS号 ]:
NI2922170

[ 海关编码 ]:
2933990090

氟吗西尼合成路线

详细合成路线

氟吗西尼上下游产品

氟吗西尼上游产品

氟吗西尼下游产品

氟吗西尼制备

方法1：5-氟靛红在冰醋酸和浓硫酸中，用30%过氧化氢氧化，得黄色固体的6-氟靛红酸酐，收率82%。然后和肌氨酸(即N-甲基甘氨酸)在二甲亚砜中，于100℃反应，得化合物(Ⅰ)，收率80%。再在氯仿中，N，N-二甲基苯胺存在下，和三氯氧磷回流。氯化所得化合物(Ⅱ)经处理后，在二甲基甲酰胺中，叔丁醇钠存在下，和氰基醋酸乙酯反应，得氟马西尼，收率40%，熔点200～203℃。
方法2：4-氟-2-(N-羧基氨基)苯甲酸和N-甲基甘氨酸环合，生成化合物(Ⅲ)，再和2-氰基乙酸乙酯环合，得到氟马西尼。

氟吗西尼海关

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

氟吗西尼文献

Tonic current through GABAA receptors and hyperpolarization-activated cyclic nucleotide-gated channels modulate resonance properties of rat subicular pyramidal neurons.

Eur. J. Neurosci. 40(1) , 2241-54, (2014)

The subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, later...

Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice.

PLoS ONE 10 , e0129150, (2015)

Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mil...

PET molecular imaging to investigate higher brain dysfunction in patients with neurotrauma.

Acta Neurochir. Suppl. 118 , 251-4, (2013)

Many neurotrauma patients suffer from higher brain dysfunction even when focal brain damage is not detected with MRI. We performed functional imaging with positron emission tomography (PET) to clarify...

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