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]
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Therapeutic Class

Hypnotics and Sedatives

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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: CHEBI:31622
CAS Number: 1622-62-4
DrugBank ID: DB01544
TTD ID: D0W2NM
INTEDE ID: DR0712

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]

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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]

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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]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Biotransformations	[13]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Biotransformations	[13]
Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1)	OTC2W96H	GBRA1_HUMAN	Protein Interaction/Cellular Processes	[14]
Gamma-aminobutyric acid receptor subunit beta-3 (GABRB3)	OT80C3D4	GBRB3_HUMAN	Protein Interaction/Cellular Processes	[14]
Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2)	OTGNDWUO	GBRG2_HUMAN	Protein Interaction/Cellular Processes	[14]
UDP-glucuronosyltransferase 1A1	OTH1C8OJ	UD11_HUMAN	Gene/Protein Processing	[15]

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Molecular Interaction Atlas (MIA)

MIA Detail

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	Evidence of significant contribution from CYP3A5 to hepatic drug metabolism. Drug Metab Dispos. 2004 Dec;32(12):1434-45. doi: 10.1124/dmd.104.001313. Epub 2004 Sep 21.
14	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.
15	Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3-hydroxydesloratadine. Biopharm Drug Dispos. 2004 Sep;25(6):243-52.