Nitrazepam

HCID 4506CAS 146-22-5

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

nitrazepamBenzalin146-22-5MogadonRadedormApodormCalsminEunoctinNeozepamNeuchlonicNitradosSonebon
Show more names
Ntz1,3-dihydro-7-nitro-5-phenyl-2h-4-benzodiazepin-2-onela1Nitrazepam (CRM)1,3-dihydro-7-nitro-5-phenyl-1,4-benzodiazepin-2-one7-Nitro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one7-Nitro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-oneLA 1Eatan
HipsalImesonRemnosSuremSomitranSonnolinTrazeninUnisomnia

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

Experimental & physicochemical properties

LogP · 2 items

2.25

2.25

LogS-3.8
Solubility · 2 items

2.99e-02 g/L

>42.2 [ug/mL] (The mean of the results at pH 7.4)

Melting Point · 2 items

225

225 °C

Physical DescriptionSolid
Kovats Retention Index · 2 items

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

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

Safety & regulation

GHS classification

GHS Classification · 5 items

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 · 2 items

DEA schedule IV controlled substance

Nitrazepam: Does not have an individual approval but may be used under an appropriate group standard

Other Safety InformationIMAP assessments - 2H-1,4-Benzodiazepin-2-one, 1,3-dihydro-7-nitro-5-phenyl-: Environment tier I assessment;IMAP assessments - 2H-1,4-Benzodiazepin-2-one, 1,3-dihydro-7-nitro-5-phenyl-: Human health tier I assessment
Hazard Classes and CategoriesAcute Tox. 4 (100%)

Toxicology

Treatment · 1 item

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 · 1 item

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.

Exposure RoutesBioavailability is 53-94% following oral administration.
Toxicity Summary · 1 item

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 · 1 item

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.

Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).

Regulatory information

Regulatory Information · 2 items

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

Chemistry & industry

Pharmacology

ATC Code · 3 items

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 · 1 item

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 · 1 item

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.

Biological Half-Life15-38 hours (mean elimination half life 26 hours).
Metabolism/MetabolitesIt is long acting, is lipophilic and is metabolised hepatically via oxidative pathways. [Wikipedia] Half Life: 15-38 hours (mean elimination half life 26 hours).
MeSH Pharmacological Classification · 4 items

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 · 2 items

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.

Use ClassificationPharmaceuticals

Applications

UsesAnticonvulsant; hypnotic. Controlled substance (depressant)

Additional notes · 1 item

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

7 records

Linked notes

Loading…