Details of the Drug

General Information of Drug (ID: DMGR5Z3)

Drug Name
Flunitrazepam
Synonyms
Flunibeta; Flunimerck; Fluninoc; Flunitrazepamum; Fluridrazepam; Narcozep; Primun; Rohipnol; Rohypnol; Roipnol; Betapharm Brand of Flunitrazepam; Ct Arzneimittel Brand of Flunitrazepam; Flunitrazepam Teva; Flunitrazepam neuraxpharm; Flunitrazepam ratiopharm; Flunizep von ct; Hexal Brand of Flunitrazepam; Merck dura Brand ofFlunitrazepam; Neuraxpharm Brand of Flunitrazepam; Ratiopharm Brand of Flunitrazepam; Roche Brand of Flunitrazepam; Teva Brand of Flunitrazepam; Fluni 1A Pharma; RO54200; [3H]flunitrazepam; Ct-Arzneimittel Brand of Flunitrazepam; Darkene (TN); Flunipam (TN); Flunitrazepam-Teva; Flunitrazepam-neuraxpharm; Flunitrazepam-ratiopharm; Flunitrazepamum [INN-Latin]; Hipnosedon (TN); Hypnodorm (TN); Ilman(TN); Insom (TN); Nilium (TN); Ro 5-4200; Rohypnol (TN); Rufinol (TN); Silece (TN); Vulbegal (TN); RO-5-4200; Flunitrazepam (JP15/USAN/INN); Flunitrazepam [USAN:INN:BAN:JAN]; 1,3-Dihydro-5-(o-fluorophenyl)-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one; 1-Methyl-7-nitro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2(1H)-one; 1A Brand of Flunitrazepam; 5-(2-Fluorophenyl)-1-methyl-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin-2-one; 5-(2-Fluorophenyl)-1-methyl-7-nitro-3H-1,4-benzodiazepin-2(1H)-one; 5-(2-fluorophenyl)-1-methyl-7-nitro-3H-1,4-benzodiazepin-2-one; 5-(o-Fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one
Indication
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [1]
Therapeutic Class
Hypnotics and Sedatives
Affected Organisms
Humans and other mammals
ATC Code
N05CD03: Flunitrazepam
N05CD: Benzodiazepine derivatives
N05C: HYPNOTICS AND SEDATIVES
N05: PSYCHOLEPTICS
N: NERVOUS SYSTEM
N05CD03: Flunitrazepam
N05CD: Benzodiazepine derivatives
N05C: HYPNOTICS AND SEDATIVES
N05: PSYCHOLEPTICS
N: NERVOUS SYSTEM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 313.28
Logarithm of the Partition Coefficient (xlogp) 2.1
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Absorption
The oral absorption of drug is 64-77% and the suppository absorption is 50% []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability
80% of drug becomes completely available to its intended biological destination(s) [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 1.4 mL/min/kg [4]
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 18 - 26 hours [4]
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 0.10629 micromolar/kg/day [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.17% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.9 L/kg [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.004 mg/mL [2]
Chemical Identifiers
Formula
C16H12FN3O3
IUPAC Name
5-(2-fluorophenyl)-1-methyl-7-nitro-3H-1,4-benzodiazepin-2-one
Canonical SMILES
CN1C(=O)CN=C(C2=C1C=CC(=C2)[N+](=O)[O-])C3=CC=CC=C3F
InChI
InChI=1S/C16H12FN3O3/c1-19-14-7-6-10(20(22)23)8-12(14)16(18-9-15(19)21)11-4-2-3-5-13(11)17/h2-8H,9H2,1H3
InChIKey
PPTYJKAXVCCBDU-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3380
ChEBI ID
CHEMBL13280
CAS Number
1622-62-4
UNII
620X0222FQ
DrugBank ID
DB01544
TTD ID
D0W2NM
INTEDE ID
DR0712
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Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Translocator protein (TSPO) TTPTXIN TSPO_HUMAN Agonist [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [8]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [9]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [10]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [8]
Oxygen-insensitive NADPH nitroreductase B (nfsB) DE0QLUZ NFSB_ECOLI Substrate [11]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Gene/Protein Processing [12]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Gene/Protein Processing [12]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Gene/Protein Processing [12]
Aldo-keto reductase family 1 member C4 (AKR1C4) OTW2MMOF AK1C4_HUMAN Gene/Protein Processing [12]
Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) OTC2W96H GBRA1_HUMAN Protein Interaction/Cellular Processes [13]
Gamma-aminobutyric acid receptor subunit beta-3 (GABRB3) OT80C3D4 GBRB3_HUMAN Protein Interaction/Cellular Processes [13]
Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2) OTGNDWUO GBRG2_HUMAN Protein Interaction/Cellular Processes [13]
UDP-glucuronosyltransferase 1A1 OTH1C8OJ UD11_HUMAN Gene/Protein Processing [14]
UDP-glucuronosyltransferase 1A3 OTUEOER3 UD13_HUMAN Gene/Protein Processing [14]
UDP-glucuronosyltransferase 2B15 OTABTFU2 UDB15_HUMAN Gene/Protein Processing [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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: 4360).
2 BDDCS applied to over 900 drugs
3 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 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
6 Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46.
7 Cytochrome P450 3A4 and benzodiazepines. Seishin Shinkeigaku Zasshi. 2003;105(5):631-42.
8 CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam. Drug Metab Dispos. 2001 Feb;29(2):133-40.
9 The role of cytochrome P450 2C19 activity in flunitrazepam metabolism in vivo. J Clin Psychopharmacol. 2003 Apr;23(2):169-75.
10 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
11 Structure-based development of bacterial nitroreductase against nitrobenzodiazepine-induced hypnosis. Biochem Pharmacol. 2012 Jun 15;83(12):1690-9.
12 Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5.
13 p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol. J Med Chem. 2011 Dec 8;54(23):8124-35. doi: 10.1021/jm200943f. Epub 2011 Nov 10.
14 Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3-hydroxydesloratadine. Biopharm Drug Dispos. 2004 Sep;25(6):243-52.