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

Details

Stereochemistry ACHIRAL
Molecular Formula C16H14ClN3O
Molecular Weight 299.7554
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHLORDIAZEPOXIDE

SMILES

CN=C1CN(=C(c2ccccc2)c3cc(ccc3N1)Cl)=O

InChI

InChIKey=ANTSCNMPPGJYLG-UHFFFAOYSA-N
InChI=1S/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9H,10H2,1H3,(H,18,19)

HIDE SMILES / InChI

Molecular Formula C16H14ClN3O
Molecular Weight 299.7554
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00136617 | https://www.drugs.com/pro/chlordiazepoxide.html | https://clinicaltrials.gov/ct2/show/NCT03012815 | https://www.ncbi.nlm.nih.gov/pubmed/6135616 | https://www.ncbi.nlm.nih.gov/pubmed/6304314

Chlordiazepoxide (trade name Librium) is a sedative and hypnotic medication of the benzodiazepine class. Chlordiazepoxide is indicated for the management of anxiety disorders or for the short-term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness of Librium in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. Chlordiazepoxide acts on benzodiazepine allosteric sites that are part of the GABAA receptor/ion-channel complex and this results in an increased binding of the inhibitory neurotransmitter GABA to the GABAA receptor thereby producing inhibitory effects on the central nervous system and body similar to the effects of other benzodiazepines. Chlordiazepoxide act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive Calcium uptake in animal nerve terminal preparations. The withdrawal of chlordiazepoxide during pregnancy and breastfeeding is recommended, as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk. Chlordiazepoxide is a long-acting benzodiazepine drug. The half-life of Chlordiazepoxide is 5 – 30 hours but has an active benzodiazepine metabolite (desmethyldiazepam), which has a half-life of 36 – 200 hours. The necessity of discontinuing therapy because of undesirable effects has been rare. Drowsiness, ataxia and confusion have been reported in some patients — particularly the elderly and debilitated. While these effects can be avoided in almost all instances by proper dosage adjustment, they have occasionally been observed at the lower dosage ranges. In a few instances syncope has been reported.

Originator

Sources: International Journal of Neuropharmacology (1955), 5, (4), 305-10

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LIBRELEASE

Approved Use

Chlordiazepoxide HCl capsules USP are indicated for the management of anxiety disorders or for the short term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness of chlordiazepoxide HCl capsules USP 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

4.32172794E11
Primary
LIBRELEASE

Approved Use

Chlordiazepoxide HCl capsules USP are indicated for the management of anxiety disorders or for the short term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness of chlordiazepoxide HCl capsules USP 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

4.32172794E11
Primary
LIBRELEASE

Approved Use

Chlordiazepoxide HCl capsules USP are indicated for the management of anxiety disorders or for the short term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness of chlordiazepoxide HCl capsules USP 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

4.32172794E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.86 μg/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE blood
Homo sapiens
population: UNKNOWN
age: ADULT
sex: MALE
food status: UNKNOWN
1.65 μg/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE blood
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.84 μg/mL
25 mg single, intramuscular
dose: 25 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.69 μg/mL
25 mg single, intramuscular
dose: 25 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7.16 μg × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
26.7 μg × h/mL
25 mg single, intramuscular
dose: 25 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
53.6 μg × h/mL
25 mg single, intramuscular
dose: 25 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.4 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
16.5 h
25 mg single, intramuscular
dose: 25 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
40.1 h
25 mg single, intramuscular
dose: 25 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
95.5%
CHLORDIAZEPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, 24-74 years
Health Status: unhealthy
Age Group: 24-74 years
Sex: M+F
Sources:
20 mg 3 times / day multiple, oral
Studied dose
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Co-administed with::
opioids
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Severe Anxiety Disorders
Age Group: adult
Sources:
Disc. AE: Sedation, Coma...
AEs leading to
discontinuation/dose reduction:
Sedation
Coma
Respiratory depression
Sources:
AEs

AEs

AESignificanceDosePopulation
Coma Disc. AE
20 mg 3 times / day multiple, oral
Studied dose
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Co-administed with::
opioids
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Severe Anxiety Disorders
Age Group: adult
Sources:
Respiratory depression Disc. AE
20 mg 3 times / day multiple, oral
Studied dose
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Co-administed with::
opioids
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Severe Anxiety Disorders
Age Group: adult
Sources:
Sedation Disc. AE
20 mg 3 times / day multiple, oral
Studied dose
Dose: 20 mg, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg, 3 times / day
Co-administed with::
opioids
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Severe Anxiety Disorders
Age Group: adult
Sources:
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Cholestatic jaundice associated with chlordiazepoxide hydrochloride (Librium) therapy. Report of a case and review of the literature.
1967 Aug
Clinical toxicity of chlordiazepoxide and diazepam in relation to serum albumin concentration: a report from the Boston Collaborative Drug Surveillance Program.
1974 Jul 26
Bromazepam, medazepam, chlordiazepoxide in treatment of neurotic anxiety.
1974 May
Hiccups following ingestion of oral chlordiazepoxide.
1976 Jun
Differential diagnosis of cimetidine-induced delirium.
1981 Mar
Opposite effects of chlordiazepoxide and serotonin receptor antagonists on morphine-induced locomotor stimulation in mice.
1982
Effect of benzodiazepines on the central action of narcotic analgesics.
1982
Acute lithium-induced tremor.
1983 Jul
Incidence and potentiation of external and internal fetal anomalies resulting from chlordiazepoxide and amitriptyline alone and in combination.
1984 Aug
Chlordiazepoxide enhances the anxiogenic action of CGS 8216 in the social interaction test: evidence for benzodiazepine withdrawal?
1985 Jul
Antagonism of drug-induced yawning and penile erections in rats.
1986 Mar 18
Hyperactivity induced by dexamphetamine/chlordiazepoxide mixtures in rats and its attenuation by lithium pretreatment: a role for dopamine?
1987
The effects of lindane, DDT, and chlordecone on avoidance responding and seizure activity.
1987 Mar 30
Inhibition of the binding and the behavioral effects of thyrotropin-releasing hormone (TRH) by the triazolobenzodiazepines.
1988 May
Reversal of increased anxiety during benzodiazepine withdrawal: evidence for an anxiogenic endogenous ligand for the benzodiazepine receptor.
1988 May
Anticonvulsive and convulsive effects of lidocaine: comparison with those of phenytoin, and implications for mechanism of action concepts.
1988 Sep
Use of receptor antagonist in elucidating the mechanism of action of TRH in GH3 cells.
1989
Evidence that the increased anxiety detected in the elevated plus-maze during chlordiazepoxide withdrawal is not due to enhanced noradrenergic activity.
1989 Dec
Caffeine-induced anxiogenesis: the role of adenosine, benzodiazepine and noradrenergic receptors.
1989 Jan
Chlordiazepoxide metabolite accumulation in liver disease.
1989 Jan-Feb
Inhibition by antimanic drugs of hyperactivity induced by methamphetamine-chlordiazepoxide mixture in mice.
1990 Apr
Expression cloning of a cDNA encoding the mouse pituitary thyrotropin-releasing hormone receptor.
1990 Dec
Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice.
1990 Jun
Absence of tumor initiating effect in the liver of rats treated with chlordiazepoxide plus sodium nitrite.
1990 Sep-Oct
Prenatal oxazepam enhances mouse maternal aggression in the offspring, without modifying acute chlordiazepoxide effects.
1991 Jan-Feb
Effects of nitrendipine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal.
1992 Jan
The attenuation of suppression of motility by triazolam in the conditioned fear stress task is exacerbated by ethanol in mice.
1995
GABA(A) receptor epsilon-subunit may confer benzodiazepine insensitivity to the caudal aspect of the nucleus tractus solitarii of the rat.
2001 Nov 1
[Determination of diazepine derivatives: alprazolam, medazepam, chlordiazepoxid mixture by high performance liquid chromatography].
2003
Anxiolytic effects of the novel anti-epileptic drug levetiracetam in the elevated plus-maze test in the rat.
2003 Nov 14
Monoterpenes affect chlorodiazepoxide-micelle interaction through micellar dipole potential modifications.
2003 Oct 13
Effects of baicalein on beta-amyloid peptide-(25-35)-induced amnesia in mice.
2004 Dec 3
Chlordiazepoxide interactions with scopolamine and dizocilpine: novel cooperative and antagonistic effects on spatial learning.
2005 Oct
Protein synthesis and the mechanisms of lasting change in anxiety induced by severe stress.
2006 Feb 28
Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress.
2007 May 16
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
2010 Dec
Acute liver failure after administration of paracetamol at the maximum recommended daily dose in adults.
2010 Dec 2
Hydroxyzine for generalised anxiety disorder.
2010 Dec 8
A dopaminergic gene cluster in the prefrontal cortex predicts performance indicative of general intelligence in genetically heterogeneous mice.
2010 Nov 17
Patents

Sample Use Guides

Relief of Mild and Moderate Anxiety Disorders and Symptoms of Anxiety: 5 mg or 10 mg, 3 or 4 times daily Relief of Severe Anxiety Disorders and Symptoms of Anxiety: 20 mg or 25 mg, 3 or 4 times daily Geriatric Patients, or in the presence of debilitating disease: 5 mg, 2 to 4 times daily
Route of Administration: Oral
In Vitro Use Guide
Eight concentrations of Chlordiazepoxide were added to tubes containing rat brain membranes and [3H]diazepam at a final concentration of 4 mkM. After incubation at 30 C for 10 min, followed by 4 C for 20 min, reactions were terminated by vacuum filtration through Whatman GF/C glass-fiber filters. Nonspecific binding was determined in the presence of 4 mkM unlabeled diazepam. The IC50 of a compound was that concentration resulting in 50% inhibition of [3H]diazepam binding to the membrane fraction.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:09:56 UTC 2021
Edited
by admin
on Fri Jun 25 21:09:56 UTC 2021
Record UNII
6RZ6XEZ3CR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CHLORDIAZEPOXIDE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   VANDF   WHO-DD  
INN  
Official Name English
CHLORDIAZEPOXIDE [INN]
Common Name English
LIMBITROL DS COMPONENT CHLORDIAZEPOXIDE
Common Name English
3H-1,4-BENZODIAZEPIN-2-AMINE, 7-CHLORO-N-METHYL-5-PHENYL-, 4-OXIDE
Systematic Name English
CHLORDIAZEPOXIDE COMPONENT OF LIMBITROL DS
Common Name English
7-CHLORO-2-METHYLAMINO-5-PHENYL-3H-1,4-BENZODIAZEPINE-4-OXIDE
Systematic Name English
CHLORDIAZEPOXIDE [MART.]
Common Name English
CHLORDIAZEPOXIDE [JAN]
Common Name English
CHLORDIAZEPOXIDE [ORANGE BOOK]
Common Name English
CHLORDIAZEPOXIDE COMPONENT OF LIMBITROL
Common Name English
CHLORDIAZEPOXIDE CIV
USP-RS  
Common Name English
7-CHLORO-2-(METHYLAMINO)-5-PHENYL-3H-1,4-BENZODIAZEPINE 4-OXIDE
Systematic Name English
CHLORDIAZEPOXIDE [MI]
Common Name English
CHLORDIAZEPOXIDE [USP]
Common Name English
CHLORDIAZEPOXIDE CIV [USP-RS]
Common Name English
CHLORDIAZEPOXIDE [EP MONOGRAPH]
Common Name English
CHLORDIAZEPOXIDE [WHO-DD]
Common Name English
CHLORDIAZEPOXIDE [HSDB]
Common Name English
LIMBITROL COMPONENT CHLORDIAZEPOXIDE
Common Name English
CHLORDIAZEPOXIDE COMPONENT OF MENRIUM
Common Name English
CHLORDIAZEPOXIDE [VANDF]
Common Name English
LIBRITABS
Brand Name English
LIBRELEASE
Brand Name English
MENRIUM COMPONENT CHLORDIAZEPOXIDE
Common Name English
Classification Tree Code System Code
WHO-VATC QN05BA02
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
NDF-RT N0000007542
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
WHO-ATC N05BA02
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
NCI_THESAURUS C1012
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
LIVERTOX 192
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
DEA NO. 2744
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
NDF-RT N0000175694
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
Code System Code Type Description
DRUG BANK
DB00475
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
FDA UNII
6RZ6XEZ3CR
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
EPA CompTox
58-25-3
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
MESH
D002707
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
DRUG CENTRAL
594
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
MERCK INDEX
M3355
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
CHLORDIAZEPOXIDE
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-371-0
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
CAS
58-25-3
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
HSDB
3028
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PRIMARY
NCI_THESAURUS
C47443
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PRIMARY
RXCUI
2356
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PRIMARY RxNorm
USP_CATALOG
1109000
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PRIMARY USP-RS
LACTMED
Chlordiazepoxide
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
IUPHAR
3370
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
INN
1049
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PRIMARY
EVMPD
SUB06179MIG
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PRIMARY
ChEMBL
CHEMBL451
Created by admin on Fri Jun 25 21:09:56 UTC 2021 , Edited by admin on Fri Jun 25 21:09:56 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
BINDER->LIGAND
SALT/SOLVATE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (TLC)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC