Identification
- Summary
Flumazenil is a benzodiazepine antagonist that is used for the complete or partial reversal of the sedative effects caused by benzodiazepines in various clinical settings, such as induced general anesthesia for diagnostic and therapeutic procedures.
- Generic Name
- Flumazenil
- DrugBank Accession Number
- DB01205
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Flumazenil (DB01205)
- Weight
- Average: 303.2884
Monoisotopic: 303.101919534 - Chemical Formula
- C15H14FN3O3
- Synonyms
- Flumazenil
- Flumazenilo
- Flumazenilum
- Flumazepil
- External IDs
- Ro 15-1788
- RO 15-1788/000
- RO-15-1788
- RO-151788
- RO-1722
- RO-41-8157
- RO15-1788
Pharmacology
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Reversal of Sedation caused by benzodiazepine •••••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
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.
- Mechanism of action
Flumazenil, an imidazobenzodiazepine derivative, is a benzodiazepine antagonist. It competitively inhibits the benzodiazepine binding 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 man.
Target Actions Organism AGamma-aminobutyric acid receptor subunit gamma-2 antagonistHumans AGamma-aminobutyric acid receptor subunit alpha-5 antagonistHumans AGABA(A) Receptor positive allosteric modulatorHumans AGamma-aminobutyric acid receptor subunit alpha-1 antagonistHumans - Absorption
Not Available
- Volume of distribution
- 0.9 to 1.1 L/kg
- Protein binding
Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis.
- Metabolism
Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.
- Route of 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.
- 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).
- Clearance
- 1 L/hr/kg [healthy volunteers receiving a 5-minute infusion of a total of 1 mg]
- Adverse Effects
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In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Flumazenil which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Flumazenil which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Flumazenil which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Flumazenil which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Flumazenil which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Take separate from meals. Eating during an intravenous infusion of flumazenil increases the elimination of flumazenil, potentially through elevated hepatic blood flow.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Anexate (Hoffmann-La Roche) / Lanexat / Mazicon
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Anexate Inj 0.1mg/ml Solution 0.1 mg / mL Intravenous Hoffmann La Roche 1991-12-31 2012-05-24 Canada 
Flumazenil Injection 0.1 mg/1mL Intravenous Akorn-Strides, LLC 2008-05-13 Not applicable US 
Flumazenil Injection Solution 0.1 mg / mL Intravenous Fresenius Kabi 2007-11-05 Not applicable Canada Flumazenil Injection Solution 0.1 mg / mL Intravenous Sandoz Canada Incorporated 2004-04-21 Not applicable Canada Flumazenil Injection Sdz Solution 0.1 mg / mL Intravenous Sandoz Canada Incorporated Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Flumazenil Injection, solution 0.1 mg/1mL Intravenous Medical Purchasing Solutions, Llc 2007-01-01 Not applicable US Flumazenil Injection 0.1 mg/1mL Intravenous West Ward Pharmaceutical 2004-10-12 Not applicable US Flumazenil Injection 1 mg/10mL Intravenous General Injectables & Vaccines 2011-02-18 Not applicable US Flumazenil Injection, solution 0.1 mg/1mL Intravenous General Injectables and Vaccines, Inc. 2014-09-16 2021-11-01 US Flumazenil Injection 0.1 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2004-10-26 2012-03-31 US
Categories
- ATC Codes
- V03AB25 — Flumazenil
- Drug Categories
- Antidotes
- Benzazepines
- Benzodiazepine Antagonist
- Benzodiazepinones
- Compounds used in a research, industrial, or household setting
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Modulators
- Heterocyclic Compounds, Fused-Ring
- Miscellaneous Central Nervous System Agents
- Neurotransmitter Agents
- Protective Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as imidazo[1,5-a][1,4]benzodiazepines. These are compounds containing an imidazole ring and a 1,4-benzodiazepine ring system, both sharing one nitrogen atom.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzodiazepines
- Sub Class
- 1,4-benzodiazepines
- Direct Parent
- Imidazo[1,5-a][1,4]benzodiazepines
- Alternative Parents
- 1,4-diazepines / Carbonylimidazoles / Aryl fluorides / Benzenoids / N-substituted imidazoles / Vinylogous amides / Tertiary carboxylic acid amides / Heteroaromatic compounds / Carboxylic acid esters / Lactams show 8 more
- Substituents
- Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid / Carboxamide group / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organofluorine compound, ethyl ester, organic heterotricyclic compound, benzodiazepine (CHEBI:5103)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 40P7XK9392
- CAS number
- 78755-81-4
- InChI Key
- OFBIFZUFASYYRE-UHFFFAOYSA-N
- 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
- 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
- SMILES
- CCOC(=O)C1=C2CN(C)C(=O)C3=C(C=CC(F)=C3)N2C=N1
References
- General 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. [Article]
- Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [Article]
- 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. doi: 10.2344/0003-3006-55.3.73. [Article]
- External Links
- Human Metabolome Database
- HMDB0015336
- KEGG Drug
- D00697
- KEGG Compound
- C07825
- PubChem Compound
- 3373
- PubChem Substance
- 46507438
- ChemSpider
- 3256
- BindingDB
- 26263
- 4457
- ChEBI
- 5103
- ChEMBL
- CHEMBL407
- ZINC
- ZINC000000001464
- Therapeutic Targets Database
- DAP000685
- PharmGKB
- PA449659
- PDBe Ligand
- FYP
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Flumazenil
- PDB Entries
- 6d6t / 6d6u / 6x3u / 8bgi
- FDA label
- Download (244 KB)
- MSDS
- Download (51.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Prevention General Anesthesia 1 4 Completed Treatment Bronchoesophageal Fistula / Endobronchial Metastases / General Anesthetic Drug Adverse Reaction 1 4 Terminated Treatment Hypoactive Delirium 1 2 Completed Treatment Substance Related Disorders 1 2 Terminated Treatment Obsessive Compulsive Disorder (OCD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Akorn Inc.
- Apotex Inc.
- APP Pharmaceuticals
- A-S Medication Solutions LLC
- Baxter International Inc.
- Bedford Labs
- Ben Venue Laboratories Inc.
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- General Injectables and Vaccines Inc.
- Hikma Pharmaceuticals
- Physicians Total Care Inc.
- Sandoz
- Strides Arcolab Limited
- Teva Pharmaceutical Industries Ltd.
- West-Ward Pharmaceuticals
- Dosage Forms
Form Route Strength Injection, solution Intravenous; Parenteral 0.5 MG/5ML Injection, solution Intravenous; Parenteral 1 MG/10ML Injection, solution Parenteral Injection, solution Intravenous 0.5 mg/5ml Injection, solution Intravenous 1 mg/10ml Injection, solution Intravenous Solution Intravenous 0.500 mg Solution Intravenous 0.5 mg Injection Intravenous 0.1 mg/1mL Injection Intravenous 0.5 mg/5mL Injection Intravenous 1 mg/10mL Injection, solution Parenteral 0.1 MG/ML Injection, solution, concentrate Intravenous Injection, solution Solution Intravenous 0.1 mg / mL Injection, solution, concentrate Intravenous; Parenteral 0.1 MG/ML Injection, solution Intravenous 0.1 mg/ml Injection Parenteral 0.1 mg/ml Injection, solution, concentrate Intravenous 0.1 mg/ml Solution Intravenous 0.1 mg/ml Injection Parenteral 0.1 mg Injection, solution 0.5 mg/5ml Injection, solution 1 mg/10ml Injection, solution Intravenous 0.1 mg/1mL - Prices
Unit description Cost Unit Romazicon 0.1 mg/ml vial 25.14USD ml Flumazenil 0.1 mg/ml vial 1.63USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 201-203 °C PhysProp water solubility 128 mg/L Not Available logP 1.00 MFG DATA SHEET - Predicted Properties
Property Value Source Water Solubility 1.04 mg/mL ALOGPS logP 1.54 ALOGPS logP 1.39 Chemaxon logS -2.5 ALOGPS pKa (Strongest Basic) 2.87 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 64.43 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 87.93 m3·mol-1 Chemaxon Polarizability 29.84 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9937 Blood Brain Barrier + 0.9382 Caco-2 permeable + 0.5355 P-glycoprotein substrate Substrate 0.6137 P-glycoprotein inhibitor I Non-inhibitor 0.8502 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.7508 CYP450 2C9 substrate Non-substrate 0.8402 CYP450 2D6 substrate Non-substrate 0.8404 CYP450 3A4 substrate Substrate 0.5764 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Inhibitor 0.8995 CYP450 3A4 inhibitor Non-inhibitor 0.866 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5863 Ames test Non AMES toxic 0.6348 Carcinogenicity Non-carcinogens 0.8872 Biodegradation Not ready biodegradable 0.9928 Rat acute toxicity 1.8903 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.987 hERG inhibition (predictor II) Non-inhibitor 0.6394
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.1211091 predictedDarkChem Lite v0.1.0 [M-H]- 175.72292 predictedDeepCCS 1.0 (2019) [M+H]+ 175.0408091 predictedDarkChem Lite v0.1.0 [M+H]+ 178.08092 predictedDeepCCS 1.0 (2019) [M+Na]+ 175.0994091 predictedDarkChem Lite v0.1.0 [M+Na]+ 184.60326 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
- Gene Name
- GABRG2
- Uniprot ID
- P18507
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit gamma-2
- Molecular Weight
- 54161.78 Da
References
- Padgett CL, Lummis SC: The F-loop of the GABA A receptor gamma2 subunit contributes to benzodiazepine modulation. J Biol Chem. 2008 Feb 1;283(5):2702-8. Epub 2007 Oct 31. [Article]
- Wingrove PB, Safo P, Wheat L, Thompson SA, Wafford KA, Whiting PJ: Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors. Eur J Pharmacol. 2002 Feb 15;437(1-2):31-9. [Article]
- Whitwam JG, Amrein R: Pharmacology of flumazenil. Acta Anaesthesiol Scand Suppl. 1995;108:3-14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Transporter activity
- Specific Function
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name
- GABRA5
- Uniprot ID
- P31644
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-5
- Molecular Weight
- 52145.645 Da
References
- Clement Y, Le Guisquet AM, Venault P, Chapouthier G, Belzung C: Pharmacological alterations of anxious behaviour in mice depending on both strain and the behavioural situation. PLoS One. 2009 Nov 11;4(11):e7745. doi: 10.1371/journal.pone.0007745. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Components:
References
- ChEMBL Compound Report Card [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
- Gene Name
- GABRA1
- Uniprot ID
- P14867
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-1
- Molecular Weight
- 51801.395 Da
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Wingrove PB, Safo P, Wheat L, Thompson SA, Wafford KA, Whiting PJ: Mechanism of alpha-subunit selectivity of benzodiazepine pharmacology at gamma-aminobutyric acid type A receptors. Eur J Pharmacol. 2002 Feb 15;437(1-2):31-9. [Article]
- Whitwam JG, Amrein R: Pharmacology of flumazenil. Acta Anaesthesiol Scand Suppl. 1995;108:3-14. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55