CAS 78755-81-4|Flumazenil|ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate|Flumazenilum [Latin]|flumazenil|Flumazenilo [Spanish]|Rom...

General Information

Structure

Molecular Formula

C₁₅H₁₄FN₃O₃

Molecular Mass

303.2883632

Exact Mass

303.10191954

Charge

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

Calculated Properties

JChem

H Acceptors

H Donor

LogD (pH = 5.5)

0.32545927

LogD (pH = 7.4)

0.32786918

Log P

0.3279

Molar Refractivity

87.9286

Polarizability

29.21609

Polar Surface Area

64.43

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

1.54

LOG S

-2.46

Solubility (Water)

1.04e+00 g/l

Data Source

Academic Data

Commercial Catalog

Data Source

Names and Identifiers

Synonyms

FlumazenilFlumazenilum [Latin]Flumazenilo [Spanish]Ro15-1788FlumazenilRo 15-1788FlumazepilAnexateMaziconLanexat8-Fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic Acid Ethyl EsterRomaziconFlumenazilRo 1722Ro 41-8157Ro 15-1788/000Ro 151788

IUPAC name

ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0²,⁶]tetradeca-1(14),3,5,10,12-pentaene-5-carboxylate ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,10,12-pentaene-5-carboxylate ethyl 12-fluoro-8-methyl-9-oxo-2,4,8-triazatricyclo[8.4.0.0²,⁶]tetradeca-1(10),3,5,11,13-pentaene-5-carboxylate

IUPAC Traditional name

flumazenil

Brand Name

RomaziconMaziconLanexatFlumazepilAnexate

Names and Identifiers

Registration numbers

CAS Number

78755-81-4

PubChem SID

2427843746507438160964538

MDL Number

MFCD00242764

PubChem CID

3373

Registration numbers

Properties

Pharmacology Properties

Target

GABA transporter

Gene Information

human ... BZRAP1(9256), GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559), GABRG2(2566)rat ... Gabra2(29706), Gabrg1(140674)

Product Information

Salt Data

Free Base

Purity

>99% (HPLC)

Certificate of Analysis

Download link

Safety Information

Storage Condition

-20°C

Refrigerator

RTECS

NI2922170

German water hazard class

Personal Protective Equipment

Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Storage Temperature

2-8°C

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Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

Selleck Chemicals

S1332

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]

DrugBank

DB01205

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]

• [RxList]

• [Drugs.com]

Sigma Aldrich

F6300

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.

TRC

F500450

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

Molecule Details

References

PubChem Literature

From Data Sources

• 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

• http://en.wikipedia.org/wiki/Flumazenil

• Pole, P., et al.: Arch. Pharmacol., 316, 317 (1981)

• Timm, U., et al.: Arzneim.-Forsch., 33, 358 (1981)

• Hunkeler, W., et al.: Nature, 290, 514 (1981)

References

Bioactivity

PubChem BioAssay

Bioactivity

Data Source

Academic Data

Commercial Catalog

Names and Identifiers

Synonyms

IUPAC name

IUPAC Traditional name

flumazenil

Brand Name

RomaziconMaziconLanexatFlumazepilAnexate

Registration numbers

CAS Number

78755-81-4

PubChem SID

2427843746507438160964538

MDL Number

PubChem CID

Molecule Details

S1332

DB01205

Drug Groups

approved

Description

Indication

Pharmacology

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

Protein Binding

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

Elimination

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

• 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]

• [RxList]

• [Drugs.com]

Sigma Aldrich

F6300

TRC

F500450

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

References

PubChem Literature

From Data Sources

• 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

• http://en.wikipedia.org/wiki/Flumazenil

• Pole, P., et al.: Arch. Pharmacol., 316, 317 (1981)

• Timm, U., et al.: Arzneim.-Forsch., 33, 358 (1981)

• Hunkeler, W., et al.: Nature, 290, 514 (1981)

Bioactivity

PubChem BioAssay

Properties

Pharmacology Properties

Target

GABA transporter

Gene Information

human ... BZRAP1(9256), GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559), GABRG2(2566)rat ... Gabra2(29706), Gabrg1(140674)

Product Information

Salt Data

Free Base

Purity

>99% (HPLC)

Certificate of Analysis

Download link

Safety Information

Storage Condition

-20°C

Refrigerator

RTECS

NI2922170

German water hazard class

Personal Protective Equipment

Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Storage Temperature

2-8°C

Download link

Molecule

ID:1075