ChemicalBook > CAS DataBase List > Flumazenil

Flumazenil

Product Name
Flumazenil
CAS No.
78755-81-4
Chemical Name
Flumazenil
Synonyms
Romazicon;ethyl 8-fluoro-5-Methyl-6-oxo-5,6-dihydro-4H-benzo[f]iMidazo[1,5-a][1,4]diazepine-3-carboxylate;FMZ;YM-684;Lanexat;Mazicon;Ro 1722;ANEXATE;FLUMAZENIL;RO 15-1788
CBNumber
CB9208108
Molecular Formula
C15H14FN3O3
Formula Weight
303.29
MOL File
78755-81-4.mol
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Flumazenil Property

Melting point:
201-203°C
Boiling point:
528.0±50.0 °C(Predicted)
Density 
1.39±0.1 g/cm3(Predicted)
storage temp. 
Sealed in dry,2-8°C
solubility 
Soluble in DMSO to 25mM
form 
solid
pka
0.86±0.20(Predicted)
color 
white
Water Solubility 
128 mg/L
Merck 
14,4135
Stability:
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
CAS DataBase Reference
78755-81-4(CAS DataBase Reference)
NIST Chemistry Reference
Flumazenil(78755-81-4)
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Safety

Hazard Codes 
Xi
Risk Statements 
36/37/38
Safety Statements 
26-27-36/37/39
WGK Germany 
2
RTECS 
NI2922170
HS Code 
2933997500
Toxicity
LD50 in mice, rats (mg/kg): 4000, 1360 i.p.; 4300, 6000 orally (Hunkeler)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H303May be harmfulif swallowed

Precautionary statements

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P403Store in a well-ventilated place.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
F6300
Product name
Flumazenil
Purity
>99% (HPLC), solid
Packaging
25mg
Price
$402
Updated
2024/03/01
Sigma-Aldrich
Product number
PHR2702
Product name
Flumazenil
Purity
certified reference material, pharmaceutical secondary standard
Packaging
500MG
Price
$691
Updated
2024/03/01
Sigma-Aldrich
Product number
5.05991
Product name
Flumazenil - CAS 78755-81-4 - Calbiochem
Packaging
10mg
Price
$113
Updated
2024/03/01
Sigma-Aldrich
Product number
1273808
Product name
Flumazenil
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
200mg
Price
$2170
Updated
2024/03/01
TCI Chemical
Product number
F0958
Product name
Flumazenil
Purity
>99.0%(GC)
Packaging
25mg
Price
$91
Updated
2024/03/01
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Flumazenil Chemical Properties,Usage,Production

Description

Flumazenil is a benzodiazepine antagonist useful as a fast-acting antidote in the treatment of benzodiazepine intoxication, and in reversing the central sedative effects of benzodiazepines during anesthesia.

Chemical Properties

Flumazenil is a white to off-white crystalline compound with an octanol:buffer partition coefficient of 14 to 1 at pH 7.4. It is insoluble in water but slightly soluble in acidic aqueous solutions.

Originator

Hoffmann-La Roche (Switzerland)

Uses

Flumazenil is an imidazodiazepine which selectively blocks the central effects of classic benzodiazepines. It is used as benzodiazepine antagonist sedation reversal drug.

Definition

ChEBI: Flumazenil is an organic heterotricyclic compound that is 5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted at positions 3, 5, 6, and 8 by ethoxycarbonyl, methyl, oxo, and fluoro groups, respectively. It is used as an antidote to benzodiazepine overdose. It has a role as a GABA antagonist and an antidote to benzodiazepine poisoning. It is an ethyl ester, an organofluorine compound and an imidazobenzodiazepine.

Preparation

The Synthesis of Flumazenil

Starting with 4-fluoroaniline (15) the isatin 17 is synthesized via the Sandmeyer synthesis; isatin is then oxidized with peracetic acid to the isatoic anhydride 18. Reaction with sarcosine in DMF leads to the benzodiazepine-2,5-dione 19. This is converted to the iminochloride by reaction with POCI3 . In the key step the imidazoester is built up by reaction with deprotonated ethyl isocyanoacetate [8]. Since ethyl isocyanoacetate is not very stable, an alternative synthesis based on the synthesis of midazolam was developed for large scale-production. Tnthis synthesis diethylmalonate is used. The diester 21 is then transformed to the monoester 22 hy deethoxycarbonylation. Nitrosation and catalytic reduction lead to the amino compound 23. The final carbon atom is introduced by reaction with the orthoester.

brand name

Romazicon (Roche);Anexate.

Therapeutic Function

Benzodiazepine receptor antagonist, Anticonvulsant

Biological Activity

Flumazenil is a GABAA receptor antagonist with non-selective for α 1, α 2, α 3 or α 5 (IC50 = 2 nM in a radioligand binding assay using rat cortical synaptosomes). Flumazenil also acts as a partial agonist of GABAA receptors, decreasing the amplitude of electrically stimulated population spikes in rat hippocampal CA1 pyramidal neurons. It increases the number of entries into the open arms of the elevated plus maze in high-anxiety BALB/c, but not C57BL/6, mice when administered at doses ranging from 0.1 to 1,000 μg/kg. Flumazenil (5 and 10 mg/kg) prevents a reduction in burying behavior induced by the GABAA receptor positive allosteric modulator allopregnanolone in ovariectomized rats when administered at doses of 5 and 10 mg/kg. Formulations containing flumazenil have been used to reverse sedation induced by benzodiazepines and in the treatment of benzodiazepine overdose or withdrawal.

Pharmacokinetics

Flumazenil is a competitive antagonist at the GA BAA benzodiazepine binding site for all other ligands. I t rapidly reverses the CN S and dangerous physiological effects of benzodiazepines following iatrogenic overdose or deliberate self-harm. I t has no effect on benzodiazepine metabolism. Flumazenil is rapidly cleared from plasma and metabolised by the liver and has a very short elimination half-life (<1h). Its duration of action depends on the dose administered and the duration of action of the drug to be antagonised; repeated administration or infusions may be necessary.

Clinical Use

Reversal of sedative effects of benzodiazepines in anaesthetic, intensive care, and diagnostic procedures

Veterinary Drugs and Treatments

Flumazenil may be useful for the reversal of benzodiazepine effects after either therapeutic use or overdoses. Flumazenil may be of benefit in the treatment of encephalopathy in patients with severe hepatic failure.

Metabolism

Flumazenil is extensively metabolised in the liver.
The carboxylic acid metabolite is the main metabolite in plasma (free form) and urine (free form and its glucuronide). This main metabolite showed no benzodiazepine agonist or antagonist activity in pharmacological tests.
Flumazenil is almost completely (99%) eliminated by non-renal routes. Practically no unchanged flumazenil is excreted in the urine, suggesting complete metabolic degradation of the drug. Elimination of radiolabelled drug is essentially complete within 72 hours, with 90-95% of the radioactivity appearing in urine and 5-10% in the faeces.

storage

+4°C (desiccate)

Mode of action

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. In animal experiments the effects of compounds showing no affinity for the benzodiazepine receptor, e.g. barbiturates, ethanol, meprobamate, GABA mimetics, adenosine receptor agonists and other agents were not affected by flumazenil, but those of nonbenzodiazepine agonists of benzodiazepine receptors, such as cyclopyrrolones (e.g. zopiclone) and triazolopyridazines were blocked.

References

Flumazenil in benzodiazepine overdose
DOI:10.1503/cmaj.160357
Pharmacological uses of flumazenil in benzodiazepine use disorders: a systematic review of limited data
DOI:10.1177/0269881120981390

Flumazenil Preparation Products And Raw materials

Raw materials

6-Fluoroisatoic anhydride Hydrogen peroxide 5-Fluoroisatin N,N-Dimethylaniline Sodium tert-butoxide Anthranilic acid Sarcosine Ethyl cyanoacetate

Preparation Products

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View Lastest Price from Flumazenil manufacturers

Dorne Chemical Technology co. LTD
Product
Flumazenil 78755-81-4
Price
US $1.00/g
Min. Order
1g
Purity
99%
Supply Ability
100kg
Release date
2024-03-26
Jinan Million Pharmaceutical Co., Ltd
Product
Flumazenil 78755-81-4
Price
US $1.00-0.50/kg
Min. Order
1kg
Purity
99%
Supply Ability
200
Release date
2024-01-12
WUHAN FORTUNA CHEMICAL CO., LTD
Product
Flumazenil 78755-81-4
Price
US $0.00/g/Bag
Min. Order
10g
Purity
98.0% ~ 102.0%; USP37
Supply Ability
15kg/month
Release date
2021-06-09

78755-81-4, FlumazenilRelated Search:

Methylparaben Paraquat dichloride Acetonitrile Triethyl orthoformate Basic Violet 1 Dihydromyrcenol Methanol Ethyl formate 1-Methylimidazole Methyl acrylate Kresoxim-methyl Urethane 4H-Imidazo[1,5-a][1,4]benzodiazepine-3-carboxylicacid, 5,6-dihydro-8-hydroxy-5-methyl-6-oxo-, ethyl ester 7-Fluoro-3,4-dihydro-4-methyl-1H-1,4-benzodiazepine-2,5-dione N,N-Dimethyformamide diethy acetal Ro 15-3505 Ro 14-7437 FLUMAZENIL ACID

  • ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
  • FLUMAZENIL
  • FluMazenil USP
  • 8-FLUORO-5,6-DIHYDRO-5-METHYL-6-OXO-4H-IMIDAZO[1,5-A][1,4]BENZO-DIAZEPINE-3-CARBOXYLIC ACID ETHYL ESTER
  • 8-FLUORO-5,6-DIHYDRO-5-METHYL-6-OXO-4H-IMIDAZO[1,5-A][1,4]BENZODIAZEPINE-3-CARBOXYLIC ACID ETHYL EST
  • 4H-IMIDAZO[1,5-A][1,4]BENZODIAZEPINE-3-CARBOXYLIC ACID, 8-FLUORO-5,6-DIHYDRO-5-METHYL-6-OXO-, ETHYL ESTER
  • RO 15-1788
  • FLUMAZENIL;RO 15-1788; RO15-1788;
  • Flumazenil、Flumazepil
  • FlumazenilUsDmf
  • FMZ
  • Ethyl 8-fluoro-5，6-dihydro-5-methyl-6-oxo-4H-imidazo[1，5-α][1，4]benzodiazepine-3-carboxylate
  • Lanexat
  • Mazicon
  • Rcr-15-1788
  • Romazicon
  • ethyl 8-fluoro-5-Methyl-6-oxo-5,6-dihydro-4H-benzo[f]iMidazo[1,5-a][1,4]diazepine-3-carboxylate
  • FluMenazil
  • Ro 15-1788/000
  • Ro 1722
  • Ro 41-8157
  • FluMazenil API
  • FluMazenil(Ro 15-1788)
  • 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
  • 1-4-Amino-3-chloro-5-(trifluoromethyl)phenyl eth Flumazenil
  • Flumazenil, 99.5%
  • ethyl 8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
  • Flumazenil78755-81-4
  • Ethyl 8-fluoro-5-methyl-5,6-dihydro-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate
  • 8-Fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester
  • YM-684
  • ANEXATE
  • Flumazepil
  • Flumazenil (200 mg)
  • 8-Fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid, ethyl ester
  • 8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester
  • Flumazenil Flumazenil
  • Flumazenil &gt
  • Flumazenil USP/EP/BP
  • Flumazenil (1273808)
  • 3R)-(+)-Tartaric acid
  • Fluorine Masini
  • 4H-Imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid, 8-fluoro-5,6-dihydro-5-methyl-6-oxo-, ethyl ester
  • Flumazenil in methanol
  • 78755-81-4
  • 78755-8104
  • 78775-81-4
  • C15H14FN3O3
  • Other APIs
  • ZEBETA
  • API
  • antagonist
  • Active Pharmaceutical Ingredients
  • GABA/Glycine receptor
  • GABA
  • Amines
  • Heterocycles
  • Intermediates & Fine Chemicals