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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2019-01-11 19:35:32 UTC
HMDB IDHMDB0015336
Secondary Accession Numbers
  • HMDB15336
Metabolite Identification
Common NameFlumazenil
DescriptionFlumazenil is only found in individuals that have used or taken this drug.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, thereby reversing the effects of benzodiazepine on the central nervous system. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.
Structure
Data?1547235332
Synonyms
ValueSource
AnexateChEBI
FlumazeniloChEBI
FlumazenilumChEBI
LanexatChEBI
Anexic acidGenerator
Hoffman-la roche brand OF flumazenilMeSH
FlumazepilMeSH
RomaziconMeSH
Roche brand OF flumazenilMeSH
Hoffman la roche brand OF flumazenilMeSH
Chemical FormulaC15H14FN3O3
Average Molecular Weight303.2884
Monoisotopic Molecular Weight303.101919534
IUPAC Nameethyl 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
Traditional Nameflumazenil
CAS Registry Number78755-81-4
SMILES
CCOC(=O)C1=C2CN(C)C(=O)C3=C(C=CC(F)=C3)N2C=N1
InChI Identifier
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
InChI KeyOFBIFZUFASYYRE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub Class1,4-benzodiazepines
Direct ParentImidazo[1,5-a][1,4]benzodiazepines
Alternative Parents
Substituents
  • Imidazo[1,5-a][1,4]benzodiazepine
  • Para-diazepine
  • Imidazole-4-carbonyl group
  • Aryl fluoride
  • Aryl halide
  • Benzenoid
  • N-substituted imidazole
  • Azole
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary carboxylic acid amide
  • Imidazole
  • Carboxamide group
  • Carboxylic acid ester
  • Lactam
  • Azacycle
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Organonitrogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organofluoride
  • Organic oxygen compound
  • Organohalogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point201 - 203 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.04 g/LNot Available
LogP1.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.04 g/LALOGPS
logP1.54ALOGPS
logP0.33ChemAxon
logS-2.5ALOGPS
pKa (Strongest Basic)3.27ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area64.43 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity87.93 m³·mol⁻¹ChemAxon
Polarizability29.97 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-3490000000-d0d0177798f08c7ec17aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0lg0-3890000000-2453b74fd469fb228589JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0kdi-1293000000-7a192ee695af1d78e7bdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0kdi-0193000000-a02a88da5dbc9ae8b8a5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0lg0-3890000000-2453b74fd469fb228589JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0039000000-512256f7d9c74da3dba9JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0pb9-2094000000-2d484b39bd1b420cc821JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-4950000000-0e25df1f3bb12b6672c9JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0zfr-2098000000-b0cd088a553670984014JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0pb9-2092000000-d4159177fc35a792370aJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a71-3790000000-b679dafe637ef0296213JSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01205 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01205 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01205
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3256
KEGG Compound IDC07825
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFlumazenil
METLIN IDNot Available
PubChem Compound3373
PDB IDNot Available
ChEBI ID5103
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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:17306436 ]
  2. Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [PubMed:18175099 ]
  3. 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. [PubMed:18788841 ]

Enzymes

General function:
Involved in ion transport
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:
GABRA1
Uniprot ID:
P14867
Molecular weight:
51801.4
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. 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. [PubMed:17016423 ]
  3. 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. [PubMed:19907641 ]
  4. Hosaka K, Jackson D, Pickrell JE, Heima M, Milgrom P: Flumazenil reversal of sublingual triazolam: a randomized controlled clinical trial. J Am Dent Assoc. 2009 May;140(5):559-66. [PubMed:19411525 ]
  5. 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:17306436 ]
  6. Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [PubMed:18175099 ]
  7. 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. [PubMed:18788841 ]
  8. Raffa RB, Cavallo F, Capasso A: Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists. Eur J Pharmacol. 2007 Jun 14;564(1-3):88-93. Epub 2007 Feb 16. [PubMed:17368613 ]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  10. 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. [PubMed:17974564 ]
  11. 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. [PubMed:11864636 ]
General function:
Involved in ion transport
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:
GABRA2
Uniprot ID:
P47869
Molecular weight:
51325.9
References
  1. 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. [PubMed:19907641 ]
  2. Hosaka K, Jackson D, Pickrell JE, Heima M, Milgrom P: Flumazenil reversal of sublingual triazolam: a randomized controlled clinical trial. J Am Dent Assoc. 2009 May;140(5):559-66. [PubMed:19411525 ]
  3. 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:17306436 ]
  4. Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [PubMed:18175099 ]
  5. 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. [PubMed:18788841 ]
  6. Raffa RB, Cavallo F, Capasso A: Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists. Eur J Pharmacol. 2007 Jun 14;564(1-3):88-93. Epub 2007 Feb 16. [PubMed:17368613 ]
General function:
Involved in ion transport
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:
GABRA3
Uniprot ID:
P34903
Molecular weight:
55164.1
References
  1. 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. [PubMed:19907641 ]
  2. Hosaka K, Jackson D, Pickrell JE, Heima M, Milgrom P: Flumazenil reversal of sublingual triazolam: a randomized controlled clinical trial. J Am Dent Assoc. 2009 May;140(5):559-66. [PubMed:19411525 ]
  3. 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:17306436 ]
  4. Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [PubMed:18175099 ]
  5. 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. [PubMed:18788841 ]
  6. Raffa RB, Cavallo F, Capasso A: Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists. Eur J Pharmacol. 2007 Jun 14;564(1-3):88-93. Epub 2007 Feb 16. [PubMed:17368613 ]
General function:
Involved in ion transport
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
Molecular weight:
52145.6
References
  1. 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. [PubMed:19907641 ]
  2. Hosaka K, Jackson D, Pickrell JE, Heima M, Milgrom P: Flumazenil reversal of sublingual triazolam: a randomized controlled clinical trial. J Am Dent Assoc. 2009 May;140(5):559-66. [PubMed:19411525 ]
  3. 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:17306436 ]
  4. Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [PubMed:18175099 ]
  5. 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. [PubMed:18788841 ]
  6. Raffa RB, Cavallo F, Capasso A: Flumazenil-sensitive dose-related physical dependence in planarians produced by two benzodiazepine and one non-benzodiazepine benzodiazepine-receptor agonists. Eur J Pharmacol. 2007 Jun 14;564(1-3):88-93. Epub 2007 Feb 16. [PubMed:17368613 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524 ]