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Details

Stereochemistry RACEMIC
Molecular Formula C19H14ClN2O5.Na
Molecular Weight 408.768
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OXAZEPAM MONOSODIUM SUCCINATE

SMILES

[Na+].[O-]C(=O)CCC(=O)OC1N=C(C2=CC=CC=C2)C3=C(NC1=O)C=CC(Cl)=C3

InChI

InChIKey=HLXIPDOKNUEODM-UHFFFAOYSA-M
InChI=1S/C19H15ClN2O5.Na/c20-12-6-7-14-13(10-12)17(11-4-2-1-3-5-11)22-19(18(26)21-14)27-16(25)9-8-15(23)24;/h1-7,10,19H,8-9H2,(H,21,26)(H,23,24);/q;+1/p-1

HIDE SMILES / InChI

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.

CNS Activity

Originator

Bell, S.C.|Childress, S.J.
6
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

1965
171
Targets

Targets

Primary TargetPharmacologyConditionPotency
Activator
1430
 0.5 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
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
Approved
8429
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/7981015
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/1867967
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/7981015
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/1867967
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%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/7981015
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%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/1867967
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:
https://link.springer.com/article/10.1007/s40278-017-28921-y
unknown, 30
n = 1
Health Status: unknown
Age Group: 30
Sex: M
Population Size: 1
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
Other AEs: Coma...
Other AEs:
Coma
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
200 mg single, oral
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
unhealthy, 75
n = 1
Health Status: unhealthy
Condition: depression following a coronary bypass operation
Age Group: 75
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
Other AEs: Coma, Blisters...
Other AEs:
Coma
Blisters
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
3000 mg single, oral
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
Other AEs: Drowsiness, Obtundation...
Other AEs:
Drowsiness
Obtundation
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
AEs

AEs

AESignificanceDosePopulation
Coma
4000 mg single, oral
Dose: 4000 mg
Route: oral
Route: single
Dose: 4000 mg
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
unknown, 30
n = 1
Health Status: unknown
Age Group: 30
Sex: M
Population Size: 1
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
Blisters
200 mg single, oral
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
unhealthy, 75
n = 1
Health Status: unhealthy
Condition: depression following a coronary bypass operation
Age Group: 75
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
Coma
200 mg single, oral
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
unhealthy, 75
n = 1
Health Status: unhealthy
Condition: depression following a coronary bypass operation
Age Group: 75
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/2231838/
Drowsiness
3000 mg single, oral
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
Obtundation
3000 mg single, oral
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
unknown
n = 1
Health Status: unknown
Population Size: 1
Sources:
https://link.springer.com/article/10.1007/s40278-017-28921-y
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OCT2
647
UGT1A1
418

UGT1A3
422

UGT2B7
389
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OCT2
648
 yes [Inhibition 20 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
UGT1A1
418
 yes
UGT1A3
422
 yes
UGT2B7
389
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:7823
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7823
eMolecules
592985
https://www.emolecules.com/cgi-bin/more?vid=592985
PubMed

PubMed

TitleDatePubMed
[Pharmacologic bases of use of benzodiazepines in peréinatal medicine].
1977 Jan
Floppy-infant syndrome: Is oxazepam the answer?
1977 Nov 26
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
Enhancement of GABA binding by benzodiazepines and related anxiolytics.
1983 May 6
Abstinence syndrome from therapeutic doses of oxazepam.
1983 Nov
Short-, medium-, and long-term effects of prenatal oxazepam on neurobehavioural development of mice.
1985
Tumor-promoting activity of benzodiazepine tranquilizers, diazepam and oxazepam, in mouse liver.
1986 May
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
Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers.
1992
Carcinogenicity studies of oxazepam in mice.
1994 Aug
Paranoid psychosis induced by oxymetazoline nasal spray.
1994 Feb 1
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
Nitric oxide-induced motor neuron disease in a patient with alcoholism.
1995 Apr 13
(S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7.
1995 Feb
Alcohol and benzodiazepines generate anxiety, panic and phobias.
1995 Feb
Late-onset seizures in alcohol withdrawal.
1995 Jun
Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease.
1996 Jan-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
Cardiac risk at the onset of treatment in patients treated with benzodiazepines and clozapine.
2002 Nov
Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9.
2002 Nov
Changes in global gene and protein expression during early mouse liver carcinogenesis induced by non-genotoxic model carcinogens oxazepam and Wyeth-14,643.
2003 Apr
Pulmonary embolism possibly associated with olanzapine treatment.
2003 Dec 13
Chemical-induced atrial thrombosis in NTP rodent studies.
2005
Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens.
2005 Mar
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
What every dentist should know about the "z-sedatives".
2007 Fall
The putative tumor suppressor Tsc-22 is downregulated early in chemically induced hepatocarcinogenesis and may be a suppressor of Gadd45b.
2007 Sep
Effects of the combination of metyrapone and oxazepam on cocaine and food self-administration in rats.
2008 Nov
Probable trimethoprim/sulfamethoxazole-induced higher-level gait disorder and nocturnal delirium in an elderly man.
2009 Jan
Antidepressant/anxiolytic and anti-nociceptive effects of novel 2-substituted 1,4-benzodiazepine-2-ones.
2010 Apr-Jun
Gene expression and mutation assessment provide clues of genetic and epigenetic mechanisms in liver tumors of oxazepam-exposed mice.
2011 Jul
Understanding the pharmacokinetics of anxiolytic drugs.
2013 Apr
Patents

Patents

WO/1987/000428A1
6

Sample Use Guides

In Vivo Use Guide
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).
Name Type Language
OXAZEPAM MONOSODIUM SUCCINATE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1012
Created by admin on Fri Dec 15 15:03:57 GMT 2023 , Edited by admin on Fri Dec 15 15:03:57 GMT 2023
Code System Code Type Description
FDA UNII
12HJD2925Y
Created by admin on Fri Dec 15 15:03:57 GMT 2023 , Edited by admin on Fri Dec 15 15:03:57 GMT 2023
PRIMARY
ECHA (EC/EINECS)
223-009-3
Created by admin on Fri Dec 15 15:03:57 GMT 2023 , Edited by admin on Fri Dec 15 15:03:57 GMT 2023
PRIMARY
PUBCHEM
23681176
Created by admin on Fri Dec 15 15:03:57 GMT 2023 , Edited by admin on Fri Dec 15 15:03:57 GMT 2023
PRIMARY
NCI_THESAURUS
C98138
Created by admin on Fri Dec 15 15:03:57 GMT 2023 , Edited by admin on Fri Dec 15 15:03:57 GMT 2023
PRIMARY
CAS
3693-18-3
Created by admin on Fri Dec 15 15:03:57 GMT 2023 , Edited by admin on Fri Dec 15 15:03:57 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of OXAZEPAM
NIH
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