flumazenil 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
benzodiazepine receptor antagonists/agonists (benzodiazepine derivatives) 1195 78755-81-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • flumazenil
  • anexate
  • flumazepil
  • mazicon
  • Ro-15-1788
A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.
  • Molecular weight: 303.29
  • Formula: C15H14FN3O3
  • CLOGP: 1.29
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 0
  • TPSA: 64.43
  • ALOGS: -2.46
  • ROTB: 3
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.13 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.16 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 16 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.80 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 16 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.58 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.78 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.082 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.887 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 64.269 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 13.614 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 69.320 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 77.010 % High 1
herg hERG pIC50 4.166 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 3.597 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 11.588 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 62.400 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,MAPK7,PDK1,PDK2,PIK3CD,PRKDC,TEK 16
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 1.127 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.180 High 1
mh-clint Mouse hepatocyte intrinsic clearance 35.481 High 1
mppb Mouse plasma protein binding (% unbound) 64.690 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.928 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 66.150 % High 1
rat-kpuu-brain Rat brain Kpuu 0.514 % High 1
rh-clint Rat hepatocyte intrinsic clearance 12.190 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 96.510 % High 1
rppb Rat plasma protein binding (% unbound) 54.080 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 933.254 uM High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 20, 1991 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug withdrawal convulsions 188.23 48.78 30 1242 1470 90625705
Intentional overdose 187.44 48.78 64 1208 93770 90533405
Drug dependence 103.75 48.78 31 1241 29296 90597879
Coma 97.43 48.78 37 1235 72595 90554580
Seizure 94.89 48.78 45 1227 152584 90474591
Depressed level of consciousness 93.75 48.78 36 1236 72748 90554427
Intentional product misuse 86.49 48.78 36 1236 89568 90537607
Electrocardiogram QRS complex shortened 61.68 48.78 10 1262 542 90626633
Suicide attempt 55.34 48.78 25 1247 75374 90551801

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Intentional overdose 111.64 40.24 44 1070 51412 42568809
Drug withdrawal convulsions 70.02 40.24 14 1100 1324 42618897
Coma 45.83 40.24 24 1090 53530 42566691
Intentional product misuse 45.31 40.24 25 1089 61875 42558346

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Intentional overdose 281.74 34.83 107 2371 132394 110454427
Drug withdrawal convulsions 250.67 34.83 44 2434 2405 110584416
Drug dependence 130.15 34.83 47 2431 49973 110536848
Seizure 126.55 34.83 72 2406 221113 110365708
Coma 124.44 34.83 58 2420 117811 110469010
Intentional product misuse 120.81 34.83 59 2419 132845 110453976
Depressed level of consciousness 105.46 34.83 51 2427 112227 110474594
Product use issue 70.16 34.83 57 2421 311638 110275183
Psychogenic seizure 69.79 34.83 15 2463 2349 110584472
Toxicity to various agents 68.76 34.83 68 2410 480487 110106334
Suicide attempt 68.08 34.83 37 2441 103357 110483464
Electrocardiogram QRS complex shortened 53.03 34.83 10 2468 810 110586011
Unresponsive to stimuli 50.97 34.83 26 2452 63764 110523057
Generalised tonic-clonic seizure 45.77 34.83 23 2455 54657 110532164
Electrocardiogram QRS complex prolonged 44.43 34.83 15 2463 13006 110573815
Overdose 38.82 34.83 36 2442 233758 110353063
Agitation 37.19 34.83 26 2452 113025 110473796
Hypotension 35.97 34.83 51 2427 523798 110063023
Sinus tachycardia 35.14 34.83 18 2460 44475 110542346

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC V03AB25 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Antidotes
MeSH PA D000931 Antidotes
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018682 GABA Agents
MeSH PA D018757 GABA Modulators
MeSH PA D020011 Protective Agents
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:48407 antiparkinson drug
CHEBI has role CHEBI:65259 GABA antagonist
CHEBI has role CHEBI:90757 antidote to benzodiazepine poisoning
FDA EPC N0000175680 Benzodiazepine Antagonist

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V03AB Antidotes 28 drugs
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Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Benzodiazepine Induced Sedation indication
Benzodiazepine Toxicity indication
Benzodiazepine Maintained Anesthesia indication
Anxiety contraindication 48694002
Neuromuscular block, function contraindication 55394004
Heart disease contraindication 56265001 DOID:114
Injury of head contraindication 82271004
Epilepsy contraindication 84757009 DOID:1826
Benzodiazepine dependence contraindication 231473004
Disease of liver contraindication 235856003 DOID:409
Panic disorder contraindication 371631005 DOID:594
Tricyclic Antidepressant Toxicity contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 1.93 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
GABA-A receptor alpha-2/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 9.05 WOMBAT-PK CHEMBL
GABA-A receptor alpha-3/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 8.98 WOMBAT-PK CHEMBL
GABA-A receptor alpha-5/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 9.22 WOMBAT-PK CHEMBL
GABA-A receptor alpha-1/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 9.10 WOMBAT-PK CHEMBL
GABA-A receptor alpha-6/beta-3/gamma-2 Ion channel ALLOSTERIC ANTAGONIST Ki 6.83 WOMBAT-PK CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-4 Ion channel ALLOSTERIC ANTAGONIST Ki 8.70 CHEMBL CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-1 Ion channel Kd 8.70 CHEMBL
GABA-A receptor; anion channel Ion channel Ki 9.05 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-2 Ion channel Ki 8.24 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-3 Ion channel Ki 8.09 CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-5 Ion channel Kd 9.30 CHEMBL
GABA A receptor alpha-3/beta-2/gamma-2 Ion channel Ki 9.22 CHEMBL
GABA A receptor alpha-6/beta-2/gamma-2 Ion channel Ki 7.82 CHEMBL
GABA-A receptor; alpha-1/beta-2/gamma-2 Ion channel Ki 9.30 CHEMBL
GABA-A receptor; anion channel Ion channel Ki 9.10 CHEMBL
GABA-A receptor; anion channel Ion channel Ki 10.05 CHEMBL

External reference:

IDSource
4020178 VUID
N0000148120 NUI
D00697 KEGG_DRUG
4020178 VANDF
C0016293 UMLSCUI
CHEBI:5103 CHEBI
FYP PDB_CHEM_ID
CHEMBL407 ChEMBL_ID
DB01205 DRUGBANK_ID
D005442 MESH_DESCRIPTOR_UI
3373 PUBCHEM_CID
4192 IUPHAR_LIGAND_ID
5311 INN_ID
40P7XK9392 UNII
4457 RXNORM
4736 MMSL
60236 MMSL
d01407 MMSL
003625 NDDF
387575000 SNOMEDCT_US
96247007 SNOMEDCT_US
40P7XK9392 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9683 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9684 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9783 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0143-9784 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 0404-9793 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 14 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 0404-9794 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0404-9859 INJECTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0404-9860 INJECTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 0404-9860 INJECTION 0.10 mg INTRAVENOUS ANDA 14 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 36000-148 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 36000-148 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 36000-149 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 36000-149 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 50090-1337 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1253 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 15 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1254 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 15 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1579 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 14 sections
FLUMAZENIL HUMAN PRESCRIPTION DRUG LABEL 1 51662-1699 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 52584-093 INJECTION 1 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 54868-5715 INJECTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 63323-424 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 70385-2002 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 70385-2021 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7008 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7038 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7206 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7321 INJECTION 0.10 mg INTRAVENOUS ANDA 30 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 71872-7375 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 12 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 84549-783 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections
Flumazenil HUMAN PRESCRIPTION DRUG LABEL 1 84549-784 INJECTION, SOLUTION 0.10 mg INTRAVENOUS ANDA 29 sections