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targets (6) enzymes (7)
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Identification
Name Flunitrazepam
Accession Number DB01544
Type small molecule
Groups illicit, approved
Description

A benzodiazepine with pharmacologic actions similar to those of diazepam that can cause anterograde amnesia. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Flunitrazepamum [inn-latin]
Salts Not Available
Brand names
Name Company
Narcozep
Primun
Rohypnol
Roipnol
Brand mixtures Not Available
Categories
  • Anti-anxiety Agents
  • Hypnotics and Sedatives
  • Benzodiazepines
  • GABA Modulators
CAS number 1622-62-4
Weight Average: 313.2832
Monoisotopic: 313.08626947
Chemical Formula C16H12FN3O3
InChI Key InChIKey=PPTYJKAXVCCBDU-UHFFFAOYSA-N
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
Plain Text
IUPAC Name
5-(2-fluorophenyl)-1-methyl-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
CN1C2=C(C=C(C=C2)[N+]([O-])=O)C(=NCC1=O)C1=CC=CC=C1F
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzodiazepines
  • Lactams
Substructures
  • Benzodiazepines
  • Nitrobenzenes
  • Oxoazaniums
  • Amino Ketones
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Nitro compounds
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Diazepines
  • Lactams
  • Imines
  • Aryl Halides
  • Anilines
Pharmacology
Indication For short-term treatment of severe insomnias, that are not responsive to other hypnotics.
Pharmacodynamics Flunitrazepam is a powerful hypnotic drug that is a benzodiazepine derivative. It has powerful hypnotic, sedative, anxiolytic, and skeletal muscle relaxant properties. The drug is sometimes used as a date rape drug. In the United States, the drug has not been approved by the Food and Drug Administration for medical use, and is considered to be an illegal drug. It has however been approved in the United Kingdom and other countries.
Mechanism of action Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
Absorption 50% (suppository) and 64-77% (oral)
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic.
Route of elimination Not Available
Half life 18-26 hours
Clearance Not Available
Toxicity Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 166-167 °C PhysProp
logP 2.06 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 8.58e-03 g/l ALOGPS
logP 2.2 ALOGPS
logP 2.55 ChemAxon
logS -4.6 ALOGPS
pKa (strongest basic) 1.7 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 78.49 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 82.55 ChemAxon
polarizability 29.6 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Rickels K: The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. Acta Psychiatr Scand Suppl. 1986;332:132-41. Pubmed
  2. Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. Pubmed
  3. Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. Pubmed
  4. Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: 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. Pubmed
  5. Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. Pubmed
External Links
Resource Link
KEGG Drug D01230 Link_out
PubChem Compound 3380 Link_out
PubChem Substance 46504553 Link_out
ChemSpider 3263 Link_out
BindingDB 25878 Link_out
Therapeutic Targets Database DAP000931 Link_out
PharmGKB PA164781320 Link_out
Wikipedia http://en.wikipedia.org/wiki/Flunitrazepam Link_out
ATC Codes
  • N05CD03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Clozapine Increased risk of toxicity
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid taking with grapefruit juice.
  • Take with food.
Targets

1. Translocator protein

Pharmacological action: yes
Actions: agonist

Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme

Organism class: human
UniProt ID: P30536 Link_out
Gene: TSPO Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Katz Y, Weizman R, Weizman A, Gavish M: Disulfiram and diethyldithiocarbamate are competitive inhibitors at the peripheral benzodiazepine receptor. J Pharmacol Exp Ther. 1992 Jul;262(1):394-7. Pubmed
  2. Papadopoulos V, Berkovich A, Krueger KE, Costa E, Guidotti A: Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. Endocrinology. 1991 Sep;129(3):1481-8. Pubmed
  3. Papadopoulos V, Nowzari FB, Krueger KE: Hormone-stimulated steroidogenesis is coupled to mitochondrial benzodiazepine receptors. Tropic hormone action on steroid biosynthesis is inhibited by flunitrazepam. J Biol Chem. 1991 Feb 25;266(6):3682-7. Pubmed
  4. Awad M, Gavish M: Solubilization of peripheral-type benzodiazepine binding sites from cat cerebral cortex. J Neurochem. 1989 Jun;52(6):1880-5. Pubmed
  5. Gandolfo P, Patte C, Leprince J, Thoumas JL, Vaudry H, Tonon MC: The stimulatory effect of the octadecaneuropeptide (ODN) on cytosolic Ca2+ in rat astrocytes is not mediated through classical benzodiazepine receptors. Eur J Pharmacol. 1997 Mar 19;322(2-3):275-81. Pubmed
  6. Poisnel G, Dhilly M, Le Boisselier R, Barre L, Debruyne D: Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46. Pubmed

2. Gamma-aminobutyric-acid receptor subunit alpha-2

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P47869 Link_out
Gene: GABRA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. Pubmed
  4. Oblak AL, Gibbs TT, Blatt GJ: Reduced GABA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism. Brain Res. 2010 Sep 18. Pubmed
  5. You H, Kozuska JL, Paulsen IM, Dunn SM: Benzodiazepine modulation of the rat GABAA receptor alpha4beta3gamma2L subtype expressed in Xenopus oocytes. Neuropharmacology. 2010 Nov;59(6):527-33. Epub 2010 Jul 16. Pubmed
  6. Skilbeck KJ, O’Reilly JN, Johnston GA, Hinton T: Antipsychotic drug administration differentially affects [3H]muscimol and [3H]flunitrazepam GABA receptor binding sites. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):492-8. Epub 2007 Oct 10. Pubmed

3. Gamma-aminobutyric-acid receptor subunit alpha-4

Pharmacological action: yes
Actions: agonist

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P48169 Link_out
Gene: GABRA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Oblak AL, Gibbs TT, Blatt GJ: Reduced GABA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism. Brain Res. 2010 Sep 18. Pubmed
  4. You H, Kozuska JL, Paulsen IM, Dunn SM: Benzodiazepine modulation of the rat GABAA receptor alpha4beta3gamma2L subtype expressed in Xenopus oocytes. Neuropharmacology. 2010 Nov;59(6):527-33. Epub 2010 Jul 16. Pubmed
  5. Skilbeck KJ, O’Reilly JN, Johnston GA, Hinton T: Antipsychotic drug administration differentially affects [3H]muscimol and [3H]flunitrazepam GABA receptor binding sites. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):492-8. Epub 2007 Oct 10. Pubmed

4. Gamma-aminobutyric-acid receptor subunit alpha-5

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P31644 Link_out
Gene: GABRA5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Oblak AL, Gibbs TT, Blatt GJ: Reduced GABA receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism. Brain Res. 2010 Sep 18. Pubmed
  4. You H, Kozuska JL, Paulsen IM, Dunn SM: Benzodiazepine modulation of the rat GABAA receptor alpha4beta3gamma2L subtype expressed in Xenopus oocytes. Neuropharmacology. 2010 Nov;59(6):527-33. Epub 2010 Jul 16. Pubmed

5. Gamma-aminobutyric-acid receptor subunit alpha-6

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: Q16445 Link_out
Gene: GABRA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Santhakumar V, Hanchar HJ, Wallner M, Olsen RW, Otis TS: Contributions of the GABAA receptor alpha6 subunit to phasic and tonic inhibition revealed by a naturally occurring polymorphism in the alpha6 gene. J Neurosci. 2006 Mar 22;26(12):3357-64. Pubmed
  2. You H, Kozuska JL, Paulsen IM, Dunn SM: Benzodiazepine modulation of the rat GABAA receptor alpha4beta3gamma2L subtype expressed in Xenopus oocytes. Neuropharmacology. 2010 Nov;59(6):527-33. Epub 2010 Jul 16. Pubmed
  3. Skilbeck KJ, O’Reilly JN, Johnston GA, Hinton T: Antipsychotic drug administration differentially affects [3H]muscimol and [3H]flunitrazepam GABA receptor binding sites. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):492-8. Epub 2007 Oct 10. Pubmed

6. Gamma-aminobutyric-acid receptor subunit alpha-3

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P34903 Link_out
Gene: GABRA3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. You H, Kozuska JL, Paulsen IM, Dunn SM: Benzodiazepine modulation of the rat GABAA receptor alpha4beta3gamma2L subtype expressed in Xenopus oocytes. Neuropharmacology. 2010 Nov;59(6):527-33. Epub 2010 Jul 16. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. UDP-glucuronosyltransferase 2B7

Actions: inhibitor

Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites

UniProt ID: P16662 Link_out
Gene: UGT2B7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thomassin J, Tephly TR: Photoaffinity labeling of rat liver microsomal morphine UDP-glucuronosyltransferase by [3H]flunitrazepam. Mol Pharmacol. 1990 Sep;38(3):294-8. Pubmed

3. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2A6

Actions: substrate

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2B6

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on July 31, 2007 07:10 / Updated on February 08, 2013 16:20