Details of the Drug

General Information of Drug (ID: DMPCG2L)

• Drug Name: Flumazenil
• Synonyms: flumazenil; 78755-81-4; Anexate; Flumazepil; Romazicon; Lanexat; Mazicon; Ro 15-1788; Flumazenilum; Flumazenilo; Flumazenilum [Latin]; Flumazenilo [Spanish]; Ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate; [11C]flumazenil; Ro 151788; Flumazenil (Ro 15-1788); Ro-15-1788; UNII-40P7XK9392; C15H14FN3O3; CHEMBL407; Ro15-1788; BRN 4763661; MLS000028850; Ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate; CHEBI:5103; OFBIFZUFASYYRE-UHFFFAOYSA-N; FlumUP TD; Flumazenil (transdermal patch formulation); Flumazenil (transdermal patch formulation), Coeruleus

Indication

Disease Entry	ICD 11	Status	REF
Benzodiazepine overdose	PC91	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 303.29
  Logarithm of the Partition Coefficient (xlogp); 1
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 16 mL/min/kg [3]
  Elimination: 0.5% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 40 - 80 minutes [3]
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.16486 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.58% [3]
  Vd: The volume of distribution (Vd) of drug is 0.9-1.1 L/kg []
  Water Solubility: The ability of drug to dissolve in water is measured as 0.128 mg/mL [2]
• Chemical Identifiers:
  Formula: C15H14FN3O3
  IUPAC Name: ethyl 8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
  Canonical SMILES: CCOC(=O)C1=C2CN(C(=O)C3=C(N2C=N1)C=CC(=C3)F)C
  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
  InChIKey: OFBIFZUFASYYRE-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3373
  ChEBI ID: CHEBI:5103
  CAS Number: 78755-81-4
  DrugBank ID: DB01205
  TTD ID: D0D5GD
  ACDINA ID: D01087

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GABA(A) receptor alpha-2 (GABRA2)	TTBMV1G	GBRA2_HUMAN	Modulator (allosteric modulator)	[5]
GABA(A) receptor alpha-3 (GABRA3)	TT37EDJ	GBRA3_HUMAN	Modulator (allosteric modulator)	[6]
GABA(A) receptor alpha-5 (GABRA5)	TTNZPQ1	GBRA5_HUMAN	Modulator (allosteric modulator)	[7]
GABA(A) receptor gamma-3 (GABRG3)	TTEX6LM	GBRG3_HUMAN	Modulator (allosteric modulator)	[8]
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Antagonist	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6)	OTX4UC3O	GBRA6_HUMAN	Protein Interaction/Cellular Processes	[10]
Gamma-aminobutyric acid receptor subunit beta-3 (GABRB3)	OT80C3D4	GBRB3_HUMAN	Protein Interaction/Cellular Processes	[10]
Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2)	OTGNDWUO	GBRG2_HUMAN	Protein Interaction/Cellular Processes	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Benzodiazepine overdose
• ICD Disease Classification: PC91

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Translocator protein (TSPO)	DTT	TSPO	3.93E-10	0.43	1.02
GABA(A) receptor alpha-5 (GABRA5)	DTT	GABRA5	3.15E-09	-0.68	-0.61

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Acetic acid	E00002	176	Acidulant; Buffering agent
Hydrochloric acid	E00015	313	Acidulant
methylparaben	E00149	7456	Antimicrobial preservative
Propylparaben sodium	E00567	23679044	Antimicrobial preservative
Edetate disodium	E00186	8759	Complexing agent
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Sodium hydroxide	E00234	14798	Alkalizing agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Flumazenil 1mg/10ml injectable	1mg/10ml	Injectable	Injection
Flumazenil 0.5mg/5ml injectable	0.5mg/5ml	Injectable	Injection

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4192).
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 405).
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 406).
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 408).
• [8] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 415).
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2879).
• [10] Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors. Mol Pharmacol. 1996 Feb;49(2):253-9.