flumazenil Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
benzodiazepine receptor antagonists/agonists (benzodiazepine derivatives)	1195	78755-81-4

Description:

Molecule	Description
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:

Property	Value	Reference
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

Approvals:

Date	Agency	Company	Orphan
Dec. 20, 1991	FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Drug withdrawal convulsions	187.72	54.07	30	722	1311	46683999
Intentional overdose	153.94	54.07	52	700	64892	46620418
Drug dependence	135.15	54.07	36	716	19865	46665445
Intentional product misuse	100.64	54.07	35	717	47093	46638217
Product use issue	76.96	54.07	35	717	94609	46590701
Seizure	59.60	54.07	32	720	123022	46562288

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Intentional overdose	86.50	38.21	35	793	41446	29910204
Drug withdrawal convulsions	71.27	38.21	14	814	1145	29950505
Coma	63.73	38.21	28	800	40421	29911229
Drug dependence	54.91	38.21	21	807	21274	29930376
Intentional product misuse	51.35	38.21	23	805	34644	29917006
Product use issue	42.24	38.21	22	806	45994	29905656

Pharmacologic Action:

Source	Code	Description
ATC	V03AB25	VARIOUS ALL OTHER THERAPEUTIC PRODUCTS ALL OTHER THERAPEUTIC PRODUCTS Antidotes
FDA EPC	N0000175680	Benzodiazepine Antagonist
CHEBI has role	CHEBI:65259	gamma-aminobutyric acid receptor antagonists
CHEBI has role	CHEBI:90757	antidote to benzodiazepine overdose
MeSH PA	D000931	Antidotes
MeSH PA	D018682	GABA Agents
MeSH PA	D018757	GABA Modulators
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D020011	Protective Agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
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

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	1.93	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
GABA-A receptor alpha-6/beta-3/gamma-2	Ion channel	P18507 P28472 Q16445	GBRA6_HUMAN GBRB3_HUMAN GBRG2_HUMAN	ALLOSTERIC ANTAGONIST	Ki	6.83		WOMBAT-PK	CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-4	Ion channel	P48169	GBRA4_HUMAN	ALLOSTERIC ANTAGONIST	Ki	8.70		CHEMBL	CHEMBL
GABA-A receptor alpha-1/beta-3/gamma-2	Ion channel	P14867 P18507 P28472	GBRA1_HUMAN GBRB3_HUMAN GBRG2_HUMAN	ALLOSTERIC ANTAGONIST	Ki	9.10		WOMBAT-PK	CHEMBL
GABA-A receptor alpha-2/beta-3/gamma-2	Ion channel	P18507 P28472 P47869	GBRA2_HUMAN GBRB3_HUMAN GBRG2_HUMAN	ALLOSTERIC ANTAGONIST	Ki	9.05		WOMBAT-PK	CHEMBL
GABA-A receptor alpha-3/beta-3/gamma-2	Ion channel	P18507 P28472 P34903	GBRA3_HUMAN GBRB3_HUMAN GBRG2_HUMAN	ALLOSTERIC ANTAGONIST	Ki	8.98		WOMBAT-PK	CHEMBL
GABA-A receptor alpha-5/beta-3/gamma-2	Ion channel	P18507 P28472 P31644	GBRA5_HUMAN GBRB3_HUMAN GBRG2_HUMAN	ALLOSTERIC ANTAGONIST	Ki	9.22		WOMBAT-PK	CHEMBL
GABA-A receptor; anion channel	Ion channel	O00591 O14764 P14867 P18505 P18507 P28472 P31644 P34903 P47869 P47870 P48169 P78334 Q16445 Q8N1C3 Q99928 Q9UN88	GBRA1_HUMAN GBRA2_HUMAN GBRA3_HUMAN GBRA4_HUMAN GBRA5_HUMAN GBRA6_HUMAN GBRB1_HUMAN GBRB2_HUMAN GBRB3_HUMAN GBRD_HUMAN GBRE_HUMAN GBRG1_HUMAN GBRG2_HUMAN GBRG3_HUMAN GBRP_HUMAN GBRT_HUMAN		Ki	9.05		CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-1	Ion channel	P14867	GBRA1_HUMAN		Kd	8.70		CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-2	Ion channel	P47869	GBRA2_HUMAN		Ki	8.24		CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-3	Ion channel	P34903	GBRA3_HUMAN		Ki	8.09		CHEMBL
Gamma-aminobutyric acid receptor subunit alpha-5	Ion channel	P31644	GBRA5_HUMAN		Kd	9.30		CHEMBL
GABA A receptor alpha-6/beta-2/gamma-2	Ion channel		GBRA6_RAT GBRB2_RAT GBRG2_RAT		Ki	7.82		CHEMBL
GABA-A receptor; anion channel	Ion channel		GBRA1_RAT GBRA2_RAT GBRA3_RAT GBRA4_RAT GBRA5_RAT GBRA6_RAT GBRB1_RAT GBRB2_RAT GBRB3_RAT GBRD_RAT GBRE_RAT GBRG1_RAT GBRG2_RAT GBRG3_RAT GBRP_RAT Q91ZM7_RAT		Ki	9.10		CHEMBL
GABA-A receptor; anion channel	Ion channel		GBRA1_BOVIN GBRA2_BOVIN GBRA3_BOVIN GBRA4_BOVIN GBRB1_BOVIN GBRG2_BOVIN		Ki	10.05		CHEMBL
GABA-A receptor; alpha-1/beta-2/gamma-2	Ion channel		GBRA1_RAT GBRB2_RAT GBRG2_RAT		Ki	9.30		CHEMBL
GABA A receptor alpha-3/beta-2/gamma-2	Ion channel		GBRA3_RAT GBRB2_RAT GBRG2_RAT		Ki	9.22		CHEMBL

External reference:

ID	Source
4020178	VUID
N0000148120	NUI
D00697	KEGG_DRUG
4020178	VANDF
C0591091	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

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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	0641-6031	INJECTION	0.10 mg	INTRAVENOUS	ANDA	31 sections
Flumazenil	HUMAN PRESCRIPTION DRUG LABEL	1	0641-6032	INJECTION	0.10 mg	INTRAVENOUS	ANDA	31 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	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	52584-088	INJECTION	0.10 mg	INTRAVENOUS	ANDA	13 sections
Flumazenil	HUMAN PRESCRIPTION DRUG LABEL	1	52584-089	INJECTION	0.10 mg	INTRAVENOUS	ANDA	14 sections
Flumazenil	HUMAN PRESCRIPTION DRUG LABEL	1	52584-093	INJECTION	1 mg	INTRAVENOUS	ANDA	12 sections
Flumazenil	HUMAN PRESCRIPTION DRUG LABEL	1	52584-783	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	12 sections
Flumazenil	HUMAN PRESCRIPTION DRUG LABEL	1	52584-784	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	14 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	67457-444	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	17 sections
Flumazenil	HUMAN PRESCRIPTION DRUG LABEL	1	67457-447	INJECTION, SOLUTION	0.10 mg	INTRAVENOUS	ANDA	17 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