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Identification
NameChlordiazepoxide
Accession NumberDB00475  (APRD00682)
Typesmall molecule
Groupsapproved, illicit
Description

An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
7-chloro-2-Methylamino-5-phenyl-3H-1,4-benzodiazepin-4-oxideNot AvailableNot Available
CDPNot AvailableNot Available
ChloradiazepoxideNot AvailableNot Available
Chlordiazepoxide baseNot AvailableNot Available
ChlordiazepoxidumLatinINN
ClopoxideNot AvailableNot Available
HelogaphenNot AvailableNot Available
LibritabsNot AvailableNot Available
MethaminodiazepoxideNot AvailableNot Available
MultumNot AvailableNot Available
RisolidNot AvailableNot Available
SilibrinNot AvailableNot Available
TropiumNot AvailableNot Available
Salts
Name/CAS Structure Properties
Chlordiazepoxide Hydrochloride
438-41-5
Thumb
  • InChI Key: PRNVHVUEIITLRV-UHFFFAOYSA-N
  • Monoisotopic Mass: 335.059217531
  • Average Mass: 336.216
DBSALT000632
Brand names
NameCompany
AngirexNot Available
EleniumPolfa Tarchomin
KlopoxidNycomed
LibriumAbbott
NapotonNot Available
RadepurAWD
RisolidActavis
SilibrinNot Available
SonimenNot Available
Brand mixtures
Brand NameIngredients
Apo-Chlorax CapChlordiazepoxide Hydrochloride + Clidinium Bromide
Corium CapChlordiazepoxide Hydrochloride + Clidinium Bromide
LibotrypChlordiazepoxide Hydrochloride + Amitriptyline
LibraxChlordiazepoxide Hydrochloride + Clidinium Bromide
Pro ChloraxChlordiazepoxide Hydrochloride + Clidinium Bromide
Categories
CAS number58-25-3
WeightAverage: 299.755
Monoisotopic: 299.082539792
Chemical FormulaC16H14ClN3O
InChI KeyANTSCNMPPGJYLG-UHFFFAOYSA-N
InChI
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)
IUPAC Name
7-chloro-2-(methylamino)-5-phenyl-3H-1,4$l^{5}-benzodiazepin-4-one
SMILES
CNC1=NC2=C(C=C(Cl)C=C2)C(C2=CC=CC=C2)=N(=O)C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzodiazepines
SubclassNot Available
Direct parentBenzodiazepines
Alternative parentsChlorobenzenes; Aryl Chlorides; Polyamines; Carboxamidines; Organochlorides
Substituentschlorobenzene; aryl chloride; benzene; aryl halide; polyamine; carboxylic acid amidine; amidine; organohalogen; organochloride; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
Pharmacology
IndicationFor 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.
PharmacodynamicsChlordiazepoxide has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The drug seems to block EEG arousal from stimulation in the brain stem reticular formation. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses. Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide revealed a "taming" action with the elimination of fear and aggression. The taming effect of chlordiazepoxide was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.
Mechanism of actionChlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA (A) receptor complexes at several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA(A) receptor.BZDs, therefore, enhance GABA-mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization. The net neuro-inhibitory effects result in the observed sedative, hypnotic, anxiolytic, and muscle relaxant properties.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationChlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.
Half life24-48 hours
ClearanceNot Available
ToxicityLD50=537 mg/kg (Orally in rats). Signs of overdose include respiratory depression, muscle weakness, somnolence (general depressed activity).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9758
Caco-2 permeable + 0.5868
P-glycoprotein substrate Substrate 0.6705
P-glycoprotein inhibitor I Non-inhibitor 0.521
P-glycoprotein inhibitor II Non-inhibitor 0.7434
Renal organic cation transporter Non-inhibitor 0.5502
CYP450 2C9 substrate Non-substrate 0.6991
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7408
CYP450 1A2 substrate Inhibitor 0.7564
CYP450 2C9 substrate Non-inhibitor 0.6038
CYP450 2D6 substrate Non-inhibitor 0.7862
CYP450 2C19 substrate Non-inhibitor 0.5
CYP450 3A4 substrate Inhibitor 0.7067
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6372
Ames test Non AMES toxic 0.593
Carcinogenicity Non-carcinogens 0.7108
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.8520 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9198
hERG inhibition (predictor II) Non-inhibitor 0.8828
Pharmacoeconomics
Manufacturers
  • Valeant pharmaceuticals international
  • Abbott laboratories pharmaceutical products div
  • Rachelle laboratories inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Barr laboratories inc
  • John j ferrante
  • Halsey drug co inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lederle laboratories div american cyanamid co
  • Mm mast and co
  • Mylan pharmaceuticals inc
  • Parke davis div warner lambert co
  • Pioneer pharmaceuticals inc
  • Purepac pharmaceutical co
  • Roxane laboratories inc
  • Sandoz inc
  • Superpharm corp
  • Teva pharmaceuticals usa inc
  • Usl pharma inc
  • Vangard laboratories inc div midway medical co
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Alra laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Librax 2.5-5 mg capsule6.5USDcapsule
Librax capsule5.78USDcapsule
Librium 25 mg capsule2.14USDcapsule
Limbitrol DS 10-25 mg tablet1.93USDtablet
Librium 10 mg capsule1.61USDcapsule
Librium 5 mg capsule0.84USDcapsule
Chlordiazepoxide 25 mg capsule0.72USDcapsule
ChlordiazePOXIDE HCl 25 mg capsule0.32USDcapsule
ChlordiazePOXIDE HCl 10 mg capsule0.31USDcapsule
ChlordiazePOXIDE HCl 5 mg capsule0.31USDcapsule
Chlordiazepoxide 5 mg capsule0.2USDcapsule
Apo-Chlordiazepoxide 25 mg Capsule0.17USDcapsule
Chlordiazepoxide 10 mg capsule0.14USDcapsule
Apo-Chlordiazepoxide 10 mg Capsule0.11USDcapsule
Apo-Chlordiazepoxide 5 mg Capsule0.07USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point236-236.5Sternbach, L.H.; US. Patent 2,893,992; July 7,1959; assigned to Hoffmann-LaRoche, Inc.
water solubility2000 mg/LYALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.44HANSCH,C ET AL. (1995)
pKa4.8MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
water solubility1.99e-02 g/lALOGPS
logP2.01ALOGPS
logP3.05ChemAxon
logS-4.2ALOGPS
pKa (strongest acidic)18.52ChemAxon
pKa (strongest basic)6.43ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area53.14ChemAxon
rotatable bond count1ChemAxon
refractivity87.34ChemAxon
polarizability30.97ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Sternbach, L.H.; US. Patent 2,893,992; July 7,1959; assigned to Hoffmann-LaRoche, Inc.

General Reference
  1. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. Pubmed
  2. Oishi R, Nishibori M, Itoh Y, Saeki K: Diazepam-induced decrease in histamine turnover in mouse brain. Eur J Pharmacol. 1986 May 27;124(3):337-42. Pubmed
  3. Earley JV, Fryer RI, Ning RY: Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. J Pharm Sci. 1979 Jul;68(7):845-50. Pubmed
  4. Olive G, Dreux C: [Pharmacologic bases of use of benzodiazepines in pereinatal medicine] Arch Fr Pediatr. 1977 Jan;34(1):74-89. Pubmed
  5. Vozeh S: [Pharmacokinetic of benzodiazepines in old age] Schweiz Med Wochenschr. 1981 Nov 21;111(47):1789-93. Pubmed
External Links
ResourceLink
KEGG DrugD00267
ChEBI3611
ChEMBLCHEMBL451
Therapeutic Targets DatabaseDAP000084
PharmGKBPA448932
Drug Product Database156590
RxListhttp://www.rxlist.com/cgi/generic/chlordia.htm
Drugs.comhttp://www.drugs.com/cdi/chlordiazepoxide.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lib1225.shtml
WikipediaChlordiazepoxide
ATC CodesN05BA02
AHFS Codes
  • 28:24.08
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(74.9 KB)
Interactions
Drug Interactions
Drug
CimetidineCimetidine may increase the effect of the benzodiazepine, chlordiazepoxide.
ClozapineIncreased risk of toxicity
EthotoinEthotoin may increase the metabolism of chlordiazepoxide via CYP3A4.
FluconazoleFluconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
FosphenytoinFosphenytoin may increase the metabolism of chlordiazepoxide via CYP3A4.
IndinavirThe protease inhibitor, indinavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
ItraconazoleItraconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
KavaKava may increase the effect of the benzodiazepine, chlordiazepoxide.
KetoconazoleKetoconazole may increase the effect of the benzodiazepine, chlordiazepoxide.
MephenytoinMephenytoin may increase the metabolism of chlordiazepoxide via CYP3A4.
NelfinavirThe protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
OmeprazoleOmeprazole may increase the effect of the benzodiazepine, chlordiazepoxide.
PhenytoinPhenytoin may increase the metabolism of chlordiazepoxide via CYP3A4.
RitonavirThe protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
SaquinavirThe protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, chlordiazepoxide.
TelithromycinTelithromycin may reduce clearance of Chlordiazepoxide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Chlordiazepoxide if Telithromycin is initiated, discontinued or dose changed.
TipranavirTipranavir may decrease the metabolism and clearance of Chlordiazepoxide. Consider alternate therapy or monitor for Alprazolam toxic effects if Tipranavir is initiated or dose increased.
TriprolidineThe CNS depressants, Triprolidine and Chlordiazepoxide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VoriconazoleVoriconazole may increase the serum concentration of chlordiazepoxide by decreasing its metabolism. Monitor for chlordiazepoxide toxicity if voriconazole is initiated or dose increased.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

Targets

1. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 03, 2014 16:54