U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C15H14FN3O3
Molecular Weight 303.2889
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUMAZENIL

SMILES

CCOC(=O)c1c2CN(C)C(=O)c3cc(ccc3-n2cn1)F

InChI

InChIKey=OFBIFZUFASYYRE-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/cdi/flumazenil.html

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. Fumazenil is used 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. Flumazenil went off patent in 2008 so at present generic formulations of this drug are available.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
FLUMAZENIL

Approved Use

Flumazenil Injection, USP is indicated 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, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose.

Launch Date

1.09745281E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6.98 ng/mL
2.2 mg single, sublingual
dose: 2.2 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
45.9 ng/mL
0.2 mg single, intravenous
dose: 0.2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.28 ng/mL
2.2 mg single, sublingual
dose: 2.2 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
12 ng × h/mL
2.2 mg single, sublingual
dose: 2.2 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
12.9 ng × h/mL
0.2 mg single, intravenous
dose: 0.2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.1 ng × h/mL
2.2 mg single, sublingual
dose: 2.2 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.05 h
2.2 mg single, sublingual
dose: 2.2 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.18 h
0.2 mg single, intravenous
dose: 0.2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.12 h
2.2 mg single, sublingual
dose: 2.2 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
FLUMAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
Doses

Doses

DosePopulationAdverse events​
3 mg single, intravenous
Highest studied dose
Dose: 3 mg
Route: intravenous
Route: single
Dose: 3 mg
Sources:
unhealthy, 32-62
n = 10
Health Status: unhealthy
Condition: epilepsy
Age Group: 32-62
Sex: M+F
Population Size: 10
Sources:
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Other AEs: Injection site pain, Agitation...
Other AEs:
Injection site pain (10.3%)
Agitation (8%)
Anxiety (3.4%)
Crying abnormal (3.4%)
Headache (3.4%)
Vomiting (3.4%)
Tachycardia (3.4%)
Dizziness (3.4%)
Nausea (2.3%)
Convulsions (1.1%)
Sources:
1 mg single, intravenous
Recommended
Dose: 1 mg
Route: intravenous
Route: single
Dose: 1 mg
Sources:
unhealthy, adult
n = 265
Health Status: unhealthy
Condition: hepatic encephalopathy
Age Group: adult
Sex: M+F
Population Size: 265
Sources:
AEs

AEs

AESignificanceDosePopulation
Convulsions 1.1%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Injection site pain 10.3%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Nausea 2.3%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Anxiety 3.4%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Crying abnormal 3.4%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Dizziness 3.4%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Headache 3.4%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Tachycardia 3.4%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Vomiting 3.4%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
Agitation 8%
7.13 mg single, intravenous (mean)
Recommended
Dose: 7.13 mg
Route: intravenous
Route: single
Dose: 7.13 mg
Sources:
unhealthy, 35.2 years (range: 17-75 years)
n = 87
Health Status: unhealthy
Condition: benzodiazepine overdose
Age Group: 35.2 years (range: 17-75 years)
Sex: M+F
Population Size: 87
Sources:
PubMed

PubMed

TitleDatePubMed
Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy.
2001
Different sensitivities to competitive inhibition of benzodiazepine receptor binding of 11C-iomazenil and 11C-flumazenil in rhesus monkey brain.
2001 Apr
Benzodiazepines protect against ethanol-induced gastric mucosal damage in vitro.
2001 Aug
Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae).
2001 Aug
Different types of GABA(A) receptors may mediate the anticonflict and response rate-decreasing effects of zaleplon, zolpidem, and midazolam in squirrel monkeys.
2001 Aug
Diazepam increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity by a cyclic AMP-dependent mechanism.
2001 Aug
Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections.
2001 Aug
The effects of benzodiazepines on human opioid receptor binding and function.
2001 Aug
High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.
2001 Aug
Central benzodiazepine receptors in malformations of cortical development: A quantitative study.
2001 Aug
Increase in expression of the GABA(A) receptor alpha(4) subunit gene induced by withdrawal of, but not by long-term treatment with, benzodiazepine full or partial agonists.
2001 Aug 15
Influence of benzodiazepine binding site ligands on fear-conditioned contextual memory.
2001 Aug 24
Delayed synaptic dysfunction of association cortices in carbon monoxide intoxication.
2001 Dec
Dual-[11C]tracer single-acquisition positron emission tomography studies.
2001 Dec
Chronic benzodiazepine treatment of cells expressing recombinant GABA(A) receptors uncouples allosteric binding: studies on possible mechanisms.
2001 Dec
The midazolam-induced paradox phenomenon is reversible by flumazenil. Epidemiology, patient characteristics and review of the literature.
2001 Dec
Brain function in social anxiety disorder.
2001 Dec
Involvement of benzodiazepine binding sites in an antiaggressive effect by 5-HT(1A) receptor activation in isolated mice.
2001 Dec 7
Binding of [3H]CB 34, a selective ligand for peripheral benzodiazepine receptors, to rat brain membranes.
2001 Dec 7
Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy--lomanzenil-binding in de-novo TLE.
2001 Jul
Case report of pallido-pyramidal disease with supplementary motor area involvement.
2001 Jul
Hepatic Encephalopathy.
2001 Jul
A fluorescent receptor assay for benzodiazepines using coumarin-labeled desethylflumazenil as ligand.
2001 Jul 1
Availability of antidotes at acute care hospitals in Ontario.
2001 Jul 10
Sleep inducing effects of propofol microinjection into the medial preoptic area are blocked by flumazenil.
2001 Jul 27
GABAergic and glutamatergic modulation of exploratory behavior in the dorsomedial hypothalamus.
2001 Jul-Aug
Visual event-related potentials in cirrhotic patients without overt encephalopathy: the effects of flumazenil.
2001 Jun
Interactions between LY354740, a group II metabotropic agonist and the GABA(A)-benzodiazepine receptor complex in the rat elevated plus-maze.
2001 Jun
A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia.
2001 Jun
The effects of flumazenil on sleepiness, task performance and nocturnal sleep after anesthesia with midazolam.
2001 Jun
Reversal of reserpine-induced vacuous chewing movements in rats by melatonin: involvement of peripheral benzodiazepine receptors.
2001 Jun 15
Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome.
2001 Jun 26
Modification of the effects of benzodiazepines on the exploratory behaviors of mice on a hole-board by diabetes.
2001 May
The inability of CCK to block (or CCK antagonists to substitute for) the stimulus effects of chlordiazepoxide.
2001 May-Jun
Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane-, enflurane- and isoflurane-based anesthesia.
2001 Nov
Effect of diazepam binding inhibitor (DBI) on the fluid intake, preference and the taste reactivity in mice.
2001 Nov 29
[Functional imaging (PET and SPECT) in epilepsy].
2001 Nov 4
Benzodiazepines in the intensive care unit.
2001 Oct
Benzodiazepine-GABA(A) receptor binding is very low in dysembryoplastic neuroepithelial tumor: a PET study.
2001 Oct
Prolonged vigabatrin treatment modifies developmental changes of GABA(A)-receptor binding in young children with epilepsy.
2001 Oct
[Tetraplegia in the course of coma from drug intoxication].
2001 Oct
[18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors.
2001 Oct
2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands.
2001 Oct
Synergistic interaction of diazepam with 3',5'-cyclic adenosine monophosphate-elevating agents on rat aortic rings.
2001 Oct 5
Dose-dependent enhancement of in vivo GABA(A)-benzodiazepine receptor binding by isoflurane.
2001 Sep
SPECT and neuropsychological performance in severe depression treated with ECT.
2001 Sep
Potency of positive gamma-aminobutyric acid(A) modulators to substitute for a midazolam discriminative stimulus in untreated monkeys does not predict potency to attenuate a flumazenil discriminative stimulus in diazepam-treated monkeys.
2001 Sep
Vesicular neurotransmitter transporters in Huntington's disease: initial observations and comparison with traditional synaptic markers.
2001 Sep 15
Anxiolytic effect of Kami-Shoyo-San (TJ-24) in mice: possible mediation of neurosteroid synthesis.
2001 Sep 21
Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic.
2002 Jan 2
Patents

Sample Use Guides

Usual Adult Dose for Reversal of Sedation Initial dose: 0.2 mg IV one time over 15 seconds. Repeated doses: 0.2 mg may be given every minute until the desired level of consciousness is achieved. Maximum total dose 1 mg. Most patients respond to 0.6 to 1 mg.
Route of Administration: Intravenous
Exposure (48 h) of human embryonic kidney (HEK) 293 cells stably expressing recombinant alpha1beta2gamma2S GABAA receptors to flumazenil (1 or 5 uM) in the presence of GABA (1 uM) enhanced the maximum number (Bmax) of [3H]flunitrazepam binding sites without affecting their affinity (Kd).
Name Type Language
FLUMAZENIL
EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
ANEXATE
Brand Name English
FLUMAZENIL [USAN]
Common Name English
RO-15-1788
Code English
FLUMAZENIL [MI]
Common Name English
FLUMAZEPIL
Common Name English
MAZICON
Brand Name English
FLUMAZENIL [USP-RS]
Common Name English
FLUMAZENIL [VANDF]
Common Name English
ETHYL 8-FLUORO-5,6-DIHYDRO-5-METHYL-6-OXO-4H-IMIDAZO(1,5-A)(1,4)BENZODIAZEPINE-3-CARBOXYLATE
Systematic Name English
RO-151788
Code English
FLUMAZENIL [MART.]
Common Name English
RO-151788000
Code English
NSC-759193
Code English
RO 15-1788/000
Code English
RO-1722
Code English
FLUMAZENIL [EP MONOGRAPH]
Common Name English
FLUMAZENIL [ORANGE BOOK]
Common Name English
LANEXAT
Brand Name English
FLUMAZENIL [USP MONOGRAPH]
Common Name English
ROMAZICON
Brand Name English
4H-IMIDAZO(1,5-A)(1,4)BENZODIAZEPINE-3-CARBOXYLIC ACID, 8-FLUORO-5,6-DIHYDRO-5-METHYL-6-OXO-, ETHYL ESTER
Common Name English
FLUMAZENIL [WHO-DD]
Common Name English
FLUMAZENIL [INN]
Common Name English
RO-15-1788/000
Code English
FLUMAZENIL [JAN]
Common Name English
RO-41-8157
Code English
Classification Tree Code System Code
WHO-ATC V03AB25
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
WHO-VATC QV03AB25
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
NCI_THESAURUS C1012
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
NDF-RT N0000175680
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
Code System Code Type Description
INN
5311
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
RXCUI
4457
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY RxNorm
EVMPD
SUB07693MIG
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
PUBCHEM
3373
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
MERCK INDEX
M5436
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C47534
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
EPA CompTox
78755-81-4
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
IUPHAR
4192
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
DRUG CENTRAL
1195
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
WIKIPEDIA
FLUMAZENIL
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
MESH
D005442
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
ChEMBL
CHEMBL407
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
CAS
78755-81-4
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
USP_CATALOG
1273808
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY USP-RS
DRUG BANK
DB01205
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY
FDA UNII
40P7XK9392
Created by admin on Fri Jun 25 21:03:52 UTC 2021 , Edited by admin on Fri Jun 25 21:03:52 UTC 2021
PRIMARY