U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C15H11ClN2O2.ClH
Molecular Weight 323.174
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OXAZEPAM HYDROCHLORIDE

SMILES

Cl.OC1N=C(C2=CC=CC=C2)C3=C(NC1=O)C=CC(Cl)=C3

InChI

InChIKey=PHDLSRDRRKDLQT-UHFFFAOYSA-N
InChI=1S/C15H11ClN2O2.ClH/c16-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)18-15(20)14(19)17-12;/h1-8,15,20H,(H,17,19);1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C15H11ClN2O2
Molecular Weight 286.713
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/367060 https://www.ncbi.nlm.nih.gov/pubmed/6111408

Oxazepam is the first of a chemical series of compounds, the 3-hydroxybenzodiazepinones. A therapeutic agent providing versatility and flexibility in control of common emotional disturbances, this product exerts prompt action in a wide variety of disorders associated with anxiety, tension, agitation and irritability, and anxiety associated with depression. Oxazepam has distinguished itself clinically from other benzodiazepines by virtue of its excellent tolerance. Because of its excellent tolerance, dosage is very flexible, and it is, therefore, possible to utilize oxazepam in a wide spectrum of anxiety-related disorders including the psychoses. Oxazepam has been administered to humans by the oral route only. Usual ranges for kinetic parameters are: elimination half-life, 5 to 15 hours; volume of distribution, 0.6 to 2.0 L/kg; clearance, 0.9 to 2.0 ml/min/kg. Age and liver disease have a minimal influence on oxazepam kinetics, but renal disease is associated with a prolonged half-life and increased volume of distribution.

Originator

Sources: Bell S.C., Childress S.J. (1962) A rearrangement of 5- aryl- 1,3-dihydro-2H- 1,4-benzodiazepine-2-one 4-oxides. J. Org. Chem., 27, 1691-1695.
Curator's Comment: Reference was retrieved from https://monographs.iarc.fr/ENG/Monographs/vol66/mono66-9.pdf

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.5 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
OXAZEPAM

Approved Use

Oxazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. Anxiety associated with depression is also responsive to oxazepam therapy. This product has been found particularly useful in the management of anxiety, tension, agitation and irritability in older patients. Alcoholics with acute tremulousness, inebriation, or with anxiety associated with alcohol withdrawal are responsive to therapy. The effectiveness of oxazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Launch Date

1988
Primary
OXAZEPAM

Approved Use

Oxazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. Anxiety associated with depression is also responsive to oxazepam therapy. This product has been found particularly useful in the management of anxiety, tension, agitation and irritability in older patients. Alcoholics with acute tremulousness, inebriation, or with anxiety associated with alcohol withdrawal are responsive to therapy. The effectiveness of oxazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Launch Date

1988
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
288 ng/mL
10 mg 3 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
OXAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
268 ng/mL
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OXAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4737 ng × h/mL
10 mg 3 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
OXAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.7 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OXAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
10 mg 3 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
OXAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.1%
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OXAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
4000 mg single, oral
Dose: 4000 mg
Route: oral
Route: single
Dose: 4000 mg
Sources:
unknown, 30
n = 1
Health Status: unknown
Age Group: 30
Sex: M
Population Size: 1
Sources:
Other AEs: Coma...
200 mg single, oral
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 75
n = 1
Health Status: unhealthy
Condition: depression following a coronary bypass operation
Age Group: 75
Sex: M
Population Size: 1
Sources:
Other AEs: Coma, Blisters...
Other AEs:
Coma
Blisters
Sources:
3000 mg single, oral
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
Other AEs: Drowsiness, Obtundation...
Other AEs:
Drowsiness
Obtundation
Sources:
AEs

AEs

AESignificanceDosePopulation
Coma
4000 mg single, oral
Dose: 4000 mg
Route: oral
Route: single
Dose: 4000 mg
Sources:
unknown, 30
n = 1
Health Status: unknown
Age Group: 30
Sex: M
Population Size: 1
Sources:
Blisters
200 mg single, oral
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 75
n = 1
Health Status: unhealthy
Condition: depression following a coronary bypass operation
Age Group: 75
Sex: M
Population Size: 1
Sources:
Coma
200 mg single, oral
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 75
n = 1
Health Status: unhealthy
Condition: depression following a coronary bypass operation
Age Group: 75
Sex: M
Population Size: 1
Sources:
Drowsiness
3000 mg single, oral
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
Obtundation
3000 mg single, oral
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Inhibition 20 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Seven cases of somnambulism induced by drugs.
1979 Jul
Structure activity relationships of selected benzodiazepines as anticonvulsants to local anesthetics.
1980
Oxazepam withdrawal syndrome.
1982 Apr 3
Oxazepam withdrawal syndrome.
1982 Jun 26
Enhancement of GABA binding by benzodiazepines and related anxiolytics.
1983 May 6
Abstinence syndrome from therapeutic doses of oxazepam.
1983 Nov
Acute confusional state with status petit mal as a withdrawal syndrome--and five year follow-up.
1988 Mar
Prenatal oxazepam enhances mouse maternal aggression in the offspring, without modifying acute chlordiazepoxide effects.
1991 Jan-Feb
Low frequency of H-ras mutations in hepatocellular adenomas and carcinomas and in hepatoblastomas from B6C3F1 mice exposed to oxazepam in the diet.
1994 May
(S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7.
1995 Feb
Alcohol and benzodiazepines generate anxiety, panic and phobias.
1995 Feb
Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat.
1998 Mar
Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis.
1999 Aug 19
Remission of SSRI-induced akathisia after switch to nefazodone.
2001 Jul
Cardiac risk at the onset of treatment in patients treated with benzodiazepines and clozapine.
2002 Nov
Pulmonary embolism possibly associated with olanzapine treatment.
2003 Dec 13
Oxazepam does not modulate the behavioral effects of d-amphetamine in humans.
2005 Oct
On the mechanism of hepatocarcinogenesis of benzodiazepines: evidence that diazepam and oxazepam are CYP2B inducers in rats, and both CYP2B and CYP4A inducers in mice.
2006
Large B-cell lymphoma presenting as acute abdominal pain and spontaneous splenic rupture; a case report and review of relevant literature.
2006 Nov 28
The putative tumor suppressor Tsc-22 is downregulated early in chemically induced hepatocarcinogenesis and may be a suppressor of Gadd45b.
2007 Sep
Antidepressant/anxiolytic and anti-nociceptive effects of novel 2-substituted 1,4-benzodiazepine-2-ones.
2010 Apr-Jun
Understanding the pharmacokinetics of anxiolytic drugs.
2013 Apr
Patents

Sample Use Guides

Mild-to-moderate anxiety: 10 to 15 mg, 3 or 4 times daily. Severe anxiety syndromes and Alcoholics with acute inebriation, tremulousness, or anxiety on withdrawal: 15 to 30 mg, 3 or 4 times daily. Older patients with anxiety, tension, irritability and agitation: 10 mg, 3 times daily (initial dosage), if necessary, increase cautiously to 15 mg, 3 or 4 times daily.
Route of Administration: Oral
In Vitro Use Guide
On the stretch-induced discharge activity of the isolated crayfish sensory neuron oxazepam only produced depression (less than or equal to 0.5 mM).
Substance Class Chemical
Created
by admin
on Sat Dec 16 18:30:12 GMT 2023
Edited
by admin
on Sat Dec 16 18:30:12 GMT 2023
Record UNII
ZC7746T754
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OXAZEPAM HYDROCHLORIDE
Common Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-1,3-DIHYDRO-3-HYDROXY-5-PHENYL-, HYDROCHLORIDE (1:1)
Systematic Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-1,3-DIHYDRO-3-HYDROXY-5-PHENYL-, MONOHYDROCHLORIDE
Systematic Name English
Code System Code Type Description
CAS
66017-67-2
Created by admin on Sat Dec 16 18:30:12 GMT 2023 , Edited by admin on Sat Dec 16 18:30:12 GMT 2023
PRIMARY
FDA UNII
ZC7746T754
Created by admin on Sat Dec 16 18:30:12 GMT 2023 , Edited by admin on Sat Dec 16 18:30:12 GMT 2023
PRIMARY
EPA CompTox
DTXSID501026638
Created by admin on Sat Dec 16 18:30:12 GMT 2023 , Edited by admin on Sat Dec 16 18:30:12 GMT 2023
PRIMARY
PUBCHEM
129626437
Created by admin on Sat Dec 16 18:30:12 GMT 2023 , Edited by admin on Sat Dec 16 18:30:12 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY