Identification

Name
Nitrazepam
Accession Number
DB01595
Description

A benzodiazepine derivative used as an anticonvulsant and hypnotic.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 281.2661
Monoisotopic: 281.080041233
Chemical Formula
C15H11N3O3
Synonyms
  • 1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one
  • 2,3-dihydro-7-nitro-5-phenyl-1H-1,4-benzodiazepin-2-one
  • 7-nitro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one
  • 7-nitro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
  • N-desmethylnimetazepam
  • Nitrazepam
  • Nitrazépam
  • Nitrazepamum
External IDs
  • N05CD02
  • NSC-58775
  • RO 4-5360
  • RO 5-3059

Pharmacology

Indication

Used to treat short-term sleeping problems (insomnia), such as difficulty falling asleep, frequent awakenings during the night, and early-morning awakening.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Nitrazepam is a type of benzodiazepine drug. It is a powerful hypnotic drug which possesses strong sedative, anxiolytic, amnestic, anticonvulsant, and skeletal muscle relaxant properties. Nitrazepam shortens the time required to fall asleep and lengthens the duration of sleep. It is also useful for the management of myoclonic seizures.

Mechanism of action

Nitrazepam belongs to a group of medicines called benzodiazepines. This drug affects central benzodiazepine receptors, which are associated with inhibitory GABA (gamma amino butyric acid)receptors, leading to enhanced GABA binding activity. GABA is a major neurotransmitter in the brain, which causes somnolence, relaxation of muscles, a decrease in anxiety and general central nervous system depression. Nitrazepam has anticonvulsant properties that may be attributed to its ability to bind to voltage-dependent sodium channels. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
USodium channel protein type 1 subunit alpha
other/unknown
Humans
Absorption

Bioavailability is 53-94% following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

15-38 hours (mean elimination half life 26 hours).

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

An overdose of nitrazepam may lead to impaired breathing, dizziness, decreased cognition and balance, bluish nails and lips, slurred speech, and extreme somnolence, among others. In severe overdose, these symptoms may progress to a coma with a possibility of death.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Nitrazepam can be increased when it is combined with Abametapir.
AcetaminophenNitrazepam may increase the hepatotoxic activities of Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Nitrazepam.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Nitrazepam.
AclidiniumNitrazepam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Nitrazepam is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Nitrazepam.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Nitrazepam.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Nitrazepam.
AlosetronThe risk or severity of adverse effects can be increased when Alosetron is combined with Nitrazepam.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol.
  • Limit caffeine intake.
  • Take with food.

Products

International/Other Brands
Alodorm / Apodorm / Arem / Atempol / Benzalin / Calsmin / Eatan / Eunoctin / Gerson / Hipnax / Hipsal / Ibrovek / Imeson / Imesont / Insoma / Nelbon / Nelmat / Neozepam / Neuchlonic / Nitrados / Nitrosun / Ormodon / Pacisyn / Paxadorm / Paxisyn / Pelson / Persopit / Radedorm / Relact / Remnos / Somitran / Somnite / Sonebon / Sonnolin / Surem / Trazenin / Unisomnia
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MogadonTabletOralAa Pharma Inc1980-12-31Not applicableCanada flag
MogadonTabletOralAa Pharma Inc1980-12-31Not applicableCanada flag
NitrazadonTabletOralAa Pharma Inc1996-11-082014-06-25Canada flag
NitrazadonTabletOralAa Pharma Inc1996-11-082014-06-25Canada flag
Nitrazepam-10TabletOralPro Doc Limitee2004-07-292010-07-13Canada flag
Nitrazepam-5TabletOralPro Doc Limitee2004-07-292010-07-13Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-nitrazepam Tablets BPTabletOralApotex Corporation2002-09-17Not applicableCanada flag
Apo-nitrazepam Tablets BPTabletOralApotex Corporation2002-09-17Not applicableCanada flag
Sandoz NitrazepamTabletOralSandoz Canada Incorporated1997-12-022018-08-01Canada flag
Sandoz NitrazepamTabletOralSandoz Canada Incorporated1997-12-022018-08-01Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
N05CD02 — Nitrazepam
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,4-benzodiazepines
Alternative Parents
Alpha amino acids and derivatives / Nitroaromatic compounds / Benzene and substituted derivatives / Secondary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
1,4-benzodiazepine / Allyl-type 1,3-dipolar organic compound / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / C-nitro compound / Carbonyl group / Carboxamide group / Carboxylic acid derivative
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
C-nitro compound, 1,4-benzodiazepinone (CHEBI:7581)

Chemical Identifiers

UNII
9CLV70W7HS
CAS number
146-22-5
InChI Key
KJONHKAYOJNZEC-UHFFFAOYSA-N
InChI
InChI=1S/C15H11N3O3/c19-14-9-16-15(10-4-2-1-3-5-10)12-8-11(18(20)21)6-7-13(12)17-14/h1-8H,9H2,(H,17,19)
IUPAC Name
7-nitro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
[O-][N+](=O)C1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2)C=C1

References

General References
  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:2883820]
  2. Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. [PubMed:7782744]
  3. Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines]. Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [PubMed:2570451]
  4. Podhorna J, Krsiak M: Behavioural effects of a benzodiazepine receptor partial agonist, Ro 19-8022, in the social conflict test in mice. Behav Pharmacol. 2000 Apr;11(2):143-51. [PubMed:10877119]
  5. Nowakowska E, Chodera A: Studies on the involvement of opioid mechanism in the locomotor effects of benzodiazepines in rats. Pharmacol Biochem Behav. 1991 Feb;38(2):265-6. [PubMed:1676167]
Human Metabolome Database
HMDB0015534
KEGG Drug
D00531
KEGG Compound
C07487
PubChem Compound
4506
PubChem Substance
46505806
ChemSpider
4350
BindingDB
50020856
RxNav
7440
ChEBI
7581
ChEMBL
CHEMBL13209
ZINC
ZINC000004311748
Therapeutic Targets Database
DAP000691
PharmGKB
PA10242
Wikipedia
Nitrazepam
AHFS Codes
  • 28:24.08 — Benzodiazepines

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Unknown StatusTreatmentEpilepsies1
3CompletedTreatmentSleep Initiation and Maintenance Disorders1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia1
2CompletedTreatmentEpilepsies / Infantile Spasms (IS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
Tablet10 mg/1
TabletOral5 mg
Tablet
TabletOral
Tablet10 MG
Tablet5 MG
Prices
Unit descriptionCostUnit
Mogadon 10 mg Tablet0.24USD tablet
Mogadon 5 mg Tablet0.16USD tablet
Apo-Nitrazepam 10 mg Tablet0.13USD tablet
Nitrazadon 10 mg Tablet0.11USD tablet
Sandoz Nitrazepam 10 mg Tablet0.11USD tablet
Apo-Nitrazepam 5 mg Tablet0.09USD tablet
Nitrazadon 5 mg Tablet0.08USD tablet
Sandoz Nitrazepam 5 mg Tablet0.08USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)225 °CPhysProp
logP2.25HANSCH,C ET AL. (1995)
logS-3.8ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0299 mg/mLALOGPS
logP1.95ALOGPS
logP2.55ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)11.9ChemAxon
pKa (Strongest Basic)2.61ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area87.28 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity79.22 m3·mol-1ChemAxon
Polarizability27.59 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9802
Caco-2 permeable+0.5176
P-glycoprotein substrateSubstrate0.5785
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.9205
Renal organic cation transporterNon-inhibitor0.8307
CYP450 2C9 substrateNon-substrate0.7695
CYP450 2D6 substrateNon-substrate0.8583
CYP450 3A4 substrateSubstrate0.6725
CYP450 1A2 substrateInhibitor0.7569
CYP450 2C9 inhibitorNon-inhibitor0.6133
CYP450 2D6 inhibitorNon-inhibitor0.8986
CYP450 2C19 inhibitorInhibitor0.5682
CYP450 3A4 inhibitorInhibitor0.6791
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5645
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7197
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5397 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9904
hERG inhibition (predictor II)Non-inhibitor0.8498
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0zgi-2490000000-84b5bf7df62c745f8414
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-0090000000-8f7713c4e618326c1d9b
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0090000000-d514d232dff7c473d32f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0090000000-e2a1a64f13da7ed85586
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0uk9-0190000000-f22bb948e3a20dfd2bff
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-006x-0980000000-f78bdd1a7e391dbaad48
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014l-0920000000-d334a1a23130e08b3d55
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-1900000000-3808670d5ccc91bd0e38
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0uxu-3900000000-1fc08ceb9c88d5c734ca
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-5900000000-cbcd46c7ea13a9ff18cb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00lr-0090000000-bc49e652f5e2e4f4b760
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0090000000-c63c1250878b61e6d0da
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0090000000-02d4e0b73c57e157d6b0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0019-0090000000-6623ad5dc09e01b5a573
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-0390000000-38d5874ebcc0e05f411c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-053r-0970000000-ce2d7caefc3860d70fa4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-053r-0930000000-670ac85a651f0faf0d7d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-1900000000-f96a507afa68e1b3a438
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-2900000000-c9082e2a3a5a56cfe408
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-3900000000-310a824d6452fa47d987
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0190000000-6d4a0096179c1ef67c5a
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [PubMed:23038269]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [PubMed:29950725]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [PubMed:23038269]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [PubMed:29950725]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Voltage-gated sodium channel activity
Specific Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
Gene Name
SCN1A
Uniprot ID
P35498
Uniprot Name
Sodium channel protein type 1 subunit alpha
Molecular Weight
228969.49 Da
References
  1. McLean MJ, Macdonald RL: Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther. 1988 Feb;244(2):789-95. [PubMed:2450203]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Vrzal R, Kubesova K, Pavek P, Dvorak Z: Benzodiazepines medazepam and midazolam are activators of pregnane X receptor and weak inducers of CYP3A4: investigation in primary cultures of human hepatocytes and hepatocarcinoma cell lines. Toxicol Lett. 2010 Mar 15;193(2):183-8. doi: 10.1016/j.toxlet.2010.01.004. Epub 2010 Jan 18. [PubMed:20080160]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. doi: 10.1080/004982598239579 . [PubMed:9574817]

Drug created on August 29, 2007 11:49 / Updated on October 19, 2020 07:46

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