化合物信息

ID:1075

基本信息

化学结构

MolImage

分子式

C₁₅H₁₄FN₃O₃

分子量

303.2883632

精确质量

303.10191954

电荷

0

InChI

InChI=1S/C15H14FN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3

InChIKey

OFBIFZUFASYYRE-UHFFFAOYSA-N

Canonic Smiles

CCOC(=O)c1ncn2c1CN(C)C(=O)c1c2ccc(c1)F

Isomeric Smiles

Fc1cc2c(n3c(CN(C2=O)C)c(nc3)C(=O)OCC)cc1

计算属性

JChem

质子受体

3

质子供体

0

LogD (pH = 5.5)

0.32545927

LogD (pH = 7.4)

0.32786918

Log P

0.3279

摩尔折射率

87.9286

极化性

29.21609

极化表面积

64.43

可自由旋转的化学键

3

里宾斯基五规则

true

ALOGPS 2.1

Log P

1.54

LOG S

-2.46

溶解度

1.04e+00 g/l

数据来源

名称和标识

数据登录号

化合物性质

分子相关蛋白质

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分子图谱

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描述信息

参考文献

生物活性

描述信息

Selleck Chemicals

Research Area: Neurological Disease
Biological Activity:
Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in humans. [1]

Drug Groups

approved

Description

Fumazenil is an imidazobenzodiazepine derivative and a potent benzodiazepine receptor antagonist that competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepine on the central nervous system.

Indication

For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, and where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures. Also for the management of benzodiazepine overdose as an adjunct for appropriate supportive and symptomatic measures.

Pharmacology

Flumazenil antagonizes the CNS effects produced by benzodiazepines, but does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids.

Toxicity

In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.

Half Life

Initial distribution half-life is 4 to 11 minutes and the terminal half-life is 40 to 80 minutes. Prolongation of the half-life to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes).

Protein Binding

Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis.

Elimination

Flumazenil is completely (99%) metabolized. Elimination of radiolabeled drug is essentially complete within 72 hours, with 90% to 95% of the radioactivity appearing in urine and 5% to 10% in the feces.

Distribution

* 0.9 to 1.1 L/kg

Clearance

* 1 L/hr/kg [healthy volunteers receiving a 5-minute infusion of a total of 1 mg]

References

• Ngo AS, Anthony CR, Samuel M, Wong E, Ponampalam R: Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department? Resuscitation. 2007 Jul;74(1):27-37. Epub 2007 Feb 15. [Pubmed]

• Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. [Pubmed]

• Maeda S, Miyawaki T, Higuchi H, Shimada M: Effect of flumazenil on disturbance of equilibrium function induced by midazolam. Anesth Prog. 2008 Fall;55(3):73-7. [Pubmed]

External Links

• [Wikipedia]

• [Drugs.com]

Biochem/physiol Actions
Highly specific benzodiazepine receptor antagonist.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. F6300.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. It is used as benzodiazepine antagonist.