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Identification
NameClorazepate
Accession NumberDB00628  (APRD00881)
Typesmall molecule
Groupsapproved, illicit
Description

A water-soluble benzodiazepine derivative effective in the treatment of anxiety. It has also muscle relaxant and anticonvulsant actions. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
7-chloro-2,3-dihydro-2,2-Dihydroxy-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acidNot AvailableNot Available
ClorazepateNot AvailableNot Available
Clorazepic acidNot AvailableBAN
Salts
Name/CAS Structure Properties
Clorazepate dipotassium
Thumb Not applicable DBSALT000953
Brand names
NameCompany
AnksenSanovel
CalnerMedipharm
CloranxenTeva
Clorazepatumsanofi-aventis
ClozeneWeidar
DipotAsian
FluliumPharmasant
Gen-xeneAlra
JustumSandoz
ManotranMarch
MedipaxTecnifar
MendonAbbott Japan
PolizepPolipharm
TencilanFinadiet
TrancapT P Drug
Transenesanofi-aventis
Tranxensanofi-aventis
Tranxènesanofi-aventis
TranxeneLundbeck
Tranxene T-TabLundbeck
Tranxilenesanofi-aventis
Tranxiliumsanofi-aventis
Zetran-5Masa Lab
Brand mixturesNot Available
CategoriesNot Available
CAS number23887-31-2
WeightAverage: 314.723
Monoisotopic: 314.045819935
Chemical FormulaC16H11ClN2O3
InChI KeyXDDJGVMJFWAHJX-UHFFFAOYSA-N
InChI
InChI=1S/C16H11ClN2O3/c17-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)19-14(16(21)22)15(20)18-12/h1-8,14H,(H,18,20)(H,21,22)
IUPAC Name
7-chloro-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine-3-carboxylic acid
SMILES
OC(=O)C1N=C(C2=CC=CC=C2)C2=C(NC1=O)C=CC(Cl)=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzodiazepines
SubclassNot Available
Direct parentBenzodiazepines
Alternative parentsChlorobenzenes; Aryl Chlorides; Secondary Carboxylic Acid Amides; Enolates; Carboxylic Acids; Polyamines; Organochlorides; Alcohols and Polyols
Substituentschlorobenzene; aryl chloride; aryl halide; benzene; carboxamide group; secondary carboxylic acid amide; polyamine; carboxylic acid; carboxylic acid derivative; enolate; organochloride; organohalogen; alcohol; 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 the symptoms of anxiety. Also used as adjunctive therapy in the management of partial seizures and for the symptomatic relief of acute alcohol withdrawal.
PharmacodynamicsClorazepate is a member of the group of drugs called benzodiazepines. Pharmacologically, clorazepate has the characteristics of the benzodiazepines. It has depressant effects on the central nervous system. The primary metabolite, nordiazepam, quickly appears in the blood stream. Studies in healthy men have shown that clorazenate has depressant effects on the central nervous system. Since orally administered clorazepate dipotassium is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug.
Mechanism of actionBenzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
AbsorptionRapidly absorbed following oral administration (bioavailability is 91%).
Volume of distributionNot Available
Protein bindingThe protein binding of nordiazepam in plasma is high (97-98%).
Metabolism

The drug is metabolized in the liver and excreted primarily in the urine. The primary metabolite, nordiazepam, is further metabolized by hydroxylation. The major urinary metabolite is conjugated oxazepam (3-hydroxynordiazepam), and smaller amounts of conjugated p-hydroxynordiazepam and nordiazepam are also found in the urine.

SubstrateEnzymesProduct
Clorazepate
Not Available
OxazepamDetails
Clorazepate
Not Available
3-hydroxynordiazepamDetails
Clorazepate
NordiazepamDetails
Clorazepate
Not Available
p-HydroxynordiazepamDetails
Route of eliminationThe drug is metabolized in the liver and excreted primarily in the urine.
Half lifeThe serum half-life is about 2 days. Nordiazepam, the primary metabolite, quickly appears in the blood and is eliminated from the plasma with an apparent half-life of about 40 to 50 hours.
ClearanceNot Available
ToxicityOral LD50 in rats is 1320 mg/kg. In monkeys, oral LD50 exceed 1600 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.
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 + 0.9285
Blood Brain Barrier + 0.8373
Caco-2 permeable + 0.5909
P-glycoprotein substrate Non-substrate 0.5597
P-glycoprotein inhibitor I Non-inhibitor 0.9328
P-glycoprotein inhibitor II Non-inhibitor 0.9386
Renal organic cation transporter Non-inhibitor 0.9049
CYP450 2C9 substrate Non-substrate 0.7365
CYP450 2D6 substrate Non-substrate 0.8745
CYP450 3A4 substrate Non-substrate 0.5798
CYP450 1A2 substrate Inhibitor 0.7086
CYP450 2C9 substrate Non-inhibitor 0.756
CYP450 2D6 substrate Non-inhibitor 0.819
CYP450 2C19 substrate Non-inhibitor 0.7451
CYP450 3A4 substrate Non-inhibitor 0.8333
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8165
Ames test Non AMES toxic 0.8311
Carcinogenicity Non-carcinogens 0.659
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 1.9282 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9987
hERG inhibition (predictor II) Non-inhibitor 0.9207
Pharmacoeconomics
Manufacturers
  • Able laboratories inc
  • American therapeutics inc
  • Clonmel healthcare ltd
  • Gd searle llc
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Quantum pharmics ltd
  • Sandoz inc
  • Usl pharma inc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
  • Lundbeck inc
  • Lederle laboratories div american cyanamid co
  • Ranbaxy laboratories ltd
  • Taro pharmaceuticals usa inc
  • Alra laboratories inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Tranxene t-tablet 15 mg5.41USDtablet
Tranxene-T 15 mg tablet5.08USDtablet
Tranxene t-tablet 7.5 mg3.99USDtablet
Tranxene-T 7.5 mg tablet3.6USDtablet
Tranxene t-tablet 3.75 mg3.21USDtablet
Tranxene-T 3.75 mg tablet3.04USDtablet
Clorazepate 15 mg tablet2.17USDtablet
Clorazepate Dipotassium 15 mg tablet1.27USDtablet
Clorazepate Dipotassium 7.5 mg tablet0.93USDtablet
Clorazepate 7.5 mg tablet0.79USDtablet
Clorazepate Dipotassium 3.75 mg tablet0.76USDtablet
Clorazepate 3.75 mg tablet0.73USDtablet
Apo-Clorazepate 15 mg Capsule0.4USDcapsule
Apo-Clorazepate 7.5 mg Capsule0.2USDcapsule
Apo-Clorazepate 3.75 mg Capsule0.15USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityVery solubleNot Available
logP3Not Available
Predicted Properties
PropertyValueSource
water solubility2.48e-02 g/lALOGPS
logP2.68ALOGPS
logP3.21ChemAxon
logS-4.1ALOGPS
pKa (strongest acidic)3.32ChemAxon
pKa (strongest basic)-0.64ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area78.76ChemAxon
rotatable bond count2ChemAxon
refractivity82.68ChemAxon
polarizability30.63ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Schmitt, J.; U.S. Patent 3,516,988; June 23, 1970.

General Reference
  1. : Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. Br Med J. 1980 Mar 29;280(6218):910-2. Pubmed
  2. McElhatton PR: The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994 Nov-Dec;8(6):461-75. Pubmed
External Links
ResourceLink
KEGG DrugD00694
PubChem Compound2809
PubChem Substance46506595
ChemSpider2707
ChEBI3761
ChEMBLCHEMBL1213252
Therapeutic Targets DatabaseDAP000240
PharmGKBPA164749297
Drug Product Database628190
RxListhttp://www.rxlist.com/cgi/generic2/clorazepate.htm
Drugs.comhttp://www.drugs.com/cdi/clorazepate.html
WikipediaClorazepate
ATC CodesN05BA05
AHFS Codes
  • 28:24.08
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmprenavirAmprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate.
CimetidineCimetidine may increase the effect of the benzodiazepine, clorazepate.
ClozapineIncreased risk of toxicity
EthotoinEthotoin may increase the metabolism of clorazepate via CYP3A4.
FluconazoleFluconazole may increase the effect of the benzodiazepine, clorazepate.
FosamprenavirFosamprenavir may increase the effect and toxicity of the benzodiazepine, clorazepate.
FosphenytoinFosphenytoin may increase the metabolism of clorazepate via CYP3A4.
IndinavirThe protease inhibitor, indinavir, may increase the effect of the benzodiazepine, clorazepate.
ItraconazoleItraconazole may increase the effect of the benzodiazepine, clorazepate.
KavaKava may increase the effect of the benzodiazepine, clorazepate.
KetoconazoleKetoconazole may increase the effect of the benzodiazepine, clorazepate.
MephenytoinMephenytoin may increase the metabolism of clorazepate via CYP3A4.
NelfinavirThe protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clorazepate.
OmeprazoleOmeprazole may increase the effect of the benzodiazepine, clorazepate.
PhenytoinPhenytoin may increase the metabolism of clorazepate via CYP3A4.
RitonavirThe protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clorazepate.
SaquinavirThe protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, clorazepate.
TelithromycinTelithromycin may reduce clearance of Clorazepate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Clorazepate if Telithromycin is initiated, discontinued or dose changed.
TipranavirTipranavir may decrease the metabolism and clearance of Clorazepate. Consider alternate therapy or monitor for Clorazepate toxic effects if Tipranavir is initiated or dose increased.
TriprolidineThe CNS depressants, Triprolidine and Clorazepate, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VoriconazoleVoriconazole may increase the serum concentration of clorazepate by decreasing its metabolism. Monitor for clorazepate 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. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. Pubmed
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. Epub 2008 Mar 31. Pubmed

2. Translocator protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Translocator protein P30536 Details

References:

  1. Park CH, Carboni E, Wood PL, Gee KW: Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line. Glia. 1996 Jan;16(1):65-70. 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. Dresser GK, Spence JD, Bailey DG: Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000 Jan;38(1):41-57. Pubmed
  2. Sachs B, Erdmann S, Al-Masaoudi T, Merk HF: In vitro drug allergy detection system incorporating human liver microsomes in chlorazepate-induced skin rash: drug-specific proliferation associated with interleukin-5 secretion. Br J Dermatol. 2001 Feb;144(2):316-20. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 08, 2014 11:29