Basic information
- Standard SMILES
O=C1CN=C(c2ccccc2)c2cc([N+](=O)[O-])ccc2N1- InChIKey
KJONHKAYOJNZEC-UHFFFAOYSA-N- Molecular formula
- C15H11N3O3
- Average molar mass
- 281.27 g/mol
- Monoisotopic mass
- 281.08004122
Names & identifiers
- Preferred name
- Nitrazepam
- IUPAC
- 7-nitro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
- English name
- Nitrazepam
- Molecular formula
- C15H11N3O3
- Molecular weight
- 281.27
Names & synonyms
Show more names
Database identifiers
- CAS
146-22-5- PubChem CID
- 4506
- DTXSID
DTXSID5023372- ChEMBL
CHEMBL13209- ChEBI
CHEBI:7581- UNII
- 9CLV70W7HS
- EC Number
- 205-665-2
- Nikkaji
- J2.956D
Properties
Computed structural properties
- XLogP
- 2.2
- Topological polar surface area
- 87.3 Ų
- Hydrogen bond donors
- 1
- Hydrogen bond acceptors
- 4
- Rotatable bonds
- 1
- Heavy atoms
- 21
- Formal charge
- 0
- Complexity
- 452
Experimental & physicochemical properties
LogP
2.25
2.25
Solubility
2.99e-02 g/L
>42.2 [ug/mL] (The mean of the results at pH 7.4)
Melting Point
225
225 °C
Kovats Retention Index
2744;2720;2740;2765;2770;2770;2770;2770;2770;2770;2770;2770;2772;2775;2777;2778;2780;2780;2780;2780
2849.9;2790.4;2755;2779.8;2820
Collision Cross Section
166.3 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]
163.6 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]
Physicochemical properties
- Melting point
- 223 · 223-227C
- Boiling point
- 423.94 °C · 423.94°C (rough estimate)
- Density
- 1.2309 · 1.2309 (rough estimate)
- refractive index
- 1.57 · 1.5700 (estimate)
- Flash point
- 2 ℃ · 2℃
- storage temp.
- -20 °C · Controlled Substance, -20°C Freezer
- solubility
- Practically insoluble in water, slightly soluble in ethanol (96 per cent).
- pka
- 2.9 · pKa 2.90 ± 0.05;10.39±0.04(H2O,t =25,I=0.015(KCl))(Approximate)
- Water Solubility
- 3.93 mg/L · 3.93mg/L(25 ºC)
- Major Application
- pharmaceutical (small molecule)
- 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)
- InChIKey
- KJONHKAYOJNZEC-UHFFFAOYSA-N
- SMILES
- [O-][N+](=O)c1ccc2NC(=O)CN=C(c3ccccc3)c2c1
- CAS DataBase Reference
- 146 · 146-22-5(CAS DataBase Reference)
- EWG's Food Scores
- 1 · 1
- FDA UNII
- 9 CLV70W7HS · 9CLV70W7HS
- ATC code
- 5 CD02 · N05CD02
- NIST Chemistry Reference
- Nitrazepam(146-22-5)
- EPA Substance Registry System
- 2 H-1,4-Benzodiazepin-2-one, · 2H-1,4-Benzodiazepin-2-one, 1,3-dihydro-7-nitro-5-phenyl- (146-22-5)
- UNSPSC Code
- 41116107 · 41116107
- NACRES
- 24 · NA.24
- Protein binding
- 87 % · 87%
- Excreted unchanged in urine
- 5 % · <5%
- Volume of distribution
- 2 · 2(L/kg)
- Biological half-life
- 24 · 24-30 / Unchanged
- Symbol(GHS)
- 7 · GHS07
- Signal word
- Warning
- Hazard statements
- 302 · H302
- Precautionary statements
- 301 · P301+P312+P330
- Hazard Codes
- Xn,F
- Risk Statements
- 22 · 22-36-20/21/22-11
- Safety Statements
- 36 · 36/37/39-36/37-16
- RIDADR
- 3249 · 3249
- WGK Germany
- 3 · 3
- RTECS
- 2450000 · DF2450000
- HazardClass
- 6.1 · 6.1(b)
- PackingGroup
- III
- Storage Class
- 11 · 11 - Combustible Solids
- Hazard Classifications
- 4 Oral · Acute Tox. 4 Oral
- Toxicity
- 50 orally · LD50 orally in rats: 825 ±80 mg/kg (Randall)
Safety & regulation
GHS classification
GHS Classification
Warning
H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 49 reports by companies from 3 notifications to the ECHA C&L Inventory.;Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.
Hazard information
Regulatory Information
DEA schedule IV controlled substance
Nitrazepam: Does not have an individual approval but may be used under an appropriate group standard
Toxicology
Treatment
General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.
Health Effects
They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
Toxicity Summary
Nitrazepam belongs to a group of medicines called benzodiazepines. It acts on benzodiazepine receptors in the brain which are associated with the GABA receptors causing an enhanced binding of GABA (gamma amino butyric acid) to GABAA receptors. GABA is a major inhibitory neurotransmitter in the brain, involved in inducing sleepiness, muscular relaxation and control of anxiety and fits, and slows down the central nervous system. The anticonvulsant properties of nitrazepam and other benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.
Signs and Symptoms
Nitrazepam is a drug which is very frequently involved in drug intoxication, including overdose. Nitrazepam overdose may result in stereotypical symptoms of benzodiazepine overdose including intoxication, impaired balance, slurred speech. In cases of severe overdose this may progress to a comatose state with the possibility of death.
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
Nitrazepam
DILI Positive
DOI:10.1016/j.drudis.2019.09.022
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation;Nitrazepam is not approved for marketing in the United States by the U.S. Food and Drug Administration. It is excreted into breastmilk in small amounts. Because of its long half-life of about 30 hours, it may accumulate in the serum of breastfed infants with repeated doses. Other agents are preferred, especially while nursing a newborn or preterm infant. If nitrazepam is used, monitor the infant for sedation, poor feeding and poor weight gain.;◉ Effects in Breastfed Infants;Relevant published information was not found as of the revision date.;◉ Effects on Lactation and Breastmilk;Relevant published information was not found as of the revision date.
Regulatory information
Regulatory Information
DEA schedule IV controlled substance
Nitrazepam: Does not have an individual approval but may be used under an appropriate group standard
Safety data
- wgk
- 3
- rtecs
- DF2450000
- ridadr
- 3249
- Toxicity
- LD50 orally in rats: 825 ±80 mg/kg (Randall)
- risk_code
- 22-36-20/21/22-11
- Signal word
- Warning
- Symbol(GHS)
- GHS07
- hazard_code
- Xn,F
- safety_code
- 36/37/39-36/37-16
- hazard_class
- 6.1(b)
- Storage Class
- 11 - Combustible Solids
- packing_group
- III
- Hazard statements
- H302
- Hazard Classifications
- Acute Tox. 4 Oral
- Precautionary statements
- P301+P312+P330
Chemistry & industry
Pharmacology
ATC Code
N05CD02
N - Nervous system;N05 - Psycholeptics;N05C - Hypnotics and sedatives;N05CD - Benzodiazepine derivatives;N05CD02 - Nitrazepam
QN - Nervous system;QN05 - Psycholeptics;QN05C - Hypnotics and sedatives;QN05CD - Benzodiazepine derivatives;QN05CD02 - Nitrazepam
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.
MeSH Pharmacological Classification
Drugs used to prevent SEIZURES or reduce their severity.
Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.
Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.
Uses & manufacturing
Uses
Use (kg; approx.) in Germany (2009): ?100;Consumption (g per capita; approx.) in Germany (2009): 0.00122;Calculated removal (%): 23.6
Used to treat short-term sleeping problems (insomnia), such as difficulty falling asleep, frequent awakenings during the night, and early-morning awakening.
Applications
UsesAnticonvulsant; hypnotic. Controlled substance (depressant)
Upstream & downstream products
Upstream raw materials
Additional notes
DefinitionChEBI: A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one which is substituted at positions 5 and 7 by phenyl and nitro groups, respectively. It is used as a hypnotic for the short-term management of insomnia and for the trea ment of epileptic spasms in infants (West's syndrome).
Related reactions
Linked notes
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