Identification

Name
Clorazepate
Accession Number
DB00628  (APRD00881)
Type
Small Molecule
Groups
Approved, 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
  • 7-chloro-2,3-dihydro-2,2-Dihydroxy-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid
  • Clorazepate
  • Clorazepic acid
External IDs
Abbott 35616 / AH 3232 / CB 4306 / Ro 6-6616 / TR 19119
Product Ingredients
IngredientUNIICASInChI Key
Clorazepate dipotassium63FN7G03XY57109-90-7QCHSEDTUUKDTIG-UHFFFAOYSA-L
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClorazepateCapsule15 mgOralAa Pharma Inc1990-12-31Not applicableCanada
ClorazepateCapsule7.5 mgOralAa Pharma Inc1990-12-31Not applicableCanada
ClorazepateCapsule3.75 mgOralAa Pharma Inc1990-12-31Not applicableCanada
Clorazepate Dipotassium T-TabTablet7.5 mg/1OralAbbvie1972-06-232018-04-30Us
Tranxene Cap 15mgCapsule15 mgOralAbbott1973-12-312003-08-01Canada
Tranxene Cap 3.75mgCapsule3.75 mgOralAbbott1973-12-312003-08-01Canada
Tranxene Cap 7.5mgCapsule7.5 mgOralAbbott1976-12-312003-08-01Canada
Tranxene T-TabTablet15 mg/1OralRECORDATI RARE DISEASES, INC.1972-06-232013-02-02Us
Tranxene T-TabTablet7.5 mg/1OralRecordati Rare Diseases Inc1972-06-23Not applicableUs
Tranxene T-TabTablet15 mg/1OralLundbeck Inc.1972-06-232013-04-12Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clorazepate DipotassiumTablet15 mg/1Oralbryant ranch prepack2000-04-27Not applicableUs63629 385920180907 15195 c3x3ck
Clorazepate DipotassiumTablet3.75 mg/1OralRebel Distributors2000-04-27Not applicableUs
Clorazepate DipotassiumTablet7.5 mg/1OralRemedy Repack2010-11-182010-11-19Us63304 0553 05 nlmimage10 d015681b
Clorazepate DipotassiumTablet3.75 mg/1OralRemedy Repack2016-07-21Not applicableUs
Clorazepate dipotassiumTablet7.5 mg/1OralRanbaxy Inc.2005-01-14Not applicableUs
Clorazepate DipotassiumTablet15 mg/1OralPhysicians Total Care, Inc.2010-08-272015-03-31Us
Clorazepate DipotassiumTablet7.5 mg/1OralContract Pharmacy Services Pa2011-03-29Not applicableUs
Clorazepate DipotassiumTablet3.75 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2000-04-27Not applicableUs51672 404220180907 15195 1hq1g48
Clorazepate DipotassiumTablet7.5 mg/1OralPd Rx Pharmaceuticals, Inc.2010-07-29Not applicableUs
Clorazepate DipotassiumTablet15 mg/1OralMylan Pharmaceuticals1987-07-17Not applicableUs
International/Other Brands
Anksen (Sanovel) / Calner (Medipharm) / Cloranxen (Teva) / Clorazepatum (sanofi-aventis) / Clozene (Weidar) / Dipot (Asian) / Flulium (Pharmasant) / Gen-xene (Alra) / Justum (Sandoz) / Manotran (March) / Medipax (Tecnifar) / Mendon (Abbott Japan) / Polizep (Polipharm) / Tencilan (Finadiet) / Trancap (T P Drug) / Transene (sanofi-aventis) / Tranxen (sanofi-aventis) / Tranxène (sanofi-aventis) / Tranxene (Lundbeck) / Tranxilene (sanofi-aventis) / Tranxilium (sanofi-aventis) / Zetran-5 (Masa Lab)
Categories
UNII
D51WO0G0L4
CAS number
23887-31-2
Weight
Average: 314.723
Monoisotopic: 314.045819935
Chemical Formula
C16H11ClN2O3
InChI Key
XDDJGVMJFWAHJX-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

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Clorazepate 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 action

Benzodiazepines 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.

TargetActionsOrganism
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
UTranslocator protein
agonist
Human
Absorption

Rapidly absorbed following oral administration (bioavailability is 91%).

Volume of distribution
Not Available
Protein binding

The 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.

Route of elimination

The drug is metabolized in the liver and excreted primarily in the urine.

Half life

The 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.

Clearance
Not Available
Toxicity

Oral 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Clorazepate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Clorazepate can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Clorazepate is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Clorazepate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Clorazepate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Clorazepate is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe therapeutic efficacy of Clorazepate can be decreased when used in combination with 6-O-benzylguanine.
7-DeazaguanineThe therapeutic efficacy of Clorazepate can be decreased when used in combination with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Clorazepate is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Clorazepate is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

References

Synthesis Reference

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

General References
  1. Authors unspecified: 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:7388368]
  2. McElhatton PR: The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994 Nov-Dec;8(6):461-75. [PubMed:7881198]
  3. Smolders EJ, de Kanter CT, de Knegt RJ, van der Valk M, Drenth JP, Burger DM: Drug-Drug Interactions Between Direct-Acting Antivirals and Psychoactive Medications. Clin Pharmacokinet. 2016 Dec;55(12):1471-1494. doi: 10.1007/s40262-016-0407-2. [PubMed:27317413]
External Links
Human Metabolome Database
HMDB0014766
KEGG Drug
D00694
KEGG Compound
C06921
PubChem Compound
2809
PubChem Substance
46506595
ChemSpider
2707
ChEBI
3761
ChEMBL
CHEMBL1213252
Therapeutic Targets Database
DAP000240
PharmGKB
PA164749297
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clorazepate
AHFS Codes
  • 28:24.08 — Benzodiazepines

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentLymphoma, T-Cell, Cutaneous / Mycosis Fungoides (MF)1
Not AvailableCompletedNot AvailableHealthy Volunteers1

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
  • Abbott Laboratories Ltd.
  • Aidarex Pharmacuticals LLC
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Corepharma LLC
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Heartland Repack Services LLC
  • Lundbeck Inc.
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Ohm Laboratories Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Qualitest
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Stat Rx Usa
  • Taro Pharmaceuticals USA
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral15 mg
CapsuleOral3.75 mg
CapsuleOral7.5 mg
TabletOral15 mg/1
TabletOral3.75 mg/1
TabletOral7.5 mg/1
Prices
Unit descriptionCostUnit
Tranxene t-tablet 15 mg5.41USD tablet
Tranxene-T 15 mg tablet5.08USD tablet
Tranxene t-tablet 7.5 mg3.99USD tablet
Tranxene-T 7.5 mg tablet3.6USD tablet
Tranxene t-tablet 3.75 mg3.21USD tablet
Tranxene-T 3.75 mg tablet3.04USD tablet
Clorazepate 15 mg tablet2.17USD tablet
Clorazepate Dipotassium 15 mg tablet1.27USD tablet
Clorazepate Dipotassium 7.5 mg tablet0.93USD tablet
Clorazepate 7.5 mg tablet0.79USD tablet
Clorazepate Dipotassium 3.75 mg tablet0.76USD tablet
Clorazepate 3.75 mg tablet0.73USD tablet
Apo-Clorazepate 15 mg Capsule0.4USD capsule
Apo-Clorazepate 7.5 mg Capsule0.2USD capsule
Apo-Clorazepate 3.75 mg Capsule0.15USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityVery solubleNot Available
logP3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0248 mg/mLALOGPS
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 Area78.76 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity82.68 m3·mol-1ChemAxon
Polarizability30.63 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9285
Blood Brain Barrier+0.8373
Caco-2 permeable+0.5909
P-glycoprotein substrateNon-substrate0.5597
P-glycoprotein inhibitor INon-inhibitor0.9328
P-glycoprotein inhibitor IINon-inhibitor0.9386
Renal organic cation transporterNon-inhibitor0.9049
CYP450 2C9 substrateNon-substrate0.7365
CYP450 2D6 substrateNon-substrate0.8745
CYP450 3A4 substrateNon-substrate0.5798
CYP450 1A2 substrateInhibitor0.7086
CYP450 2C9 inhibitorNon-inhibitor0.756
CYP450 2D6 inhibitorNon-inhibitor0.819
CYP450 2C19 inhibitorNon-inhibitor0.7451
CYP450 3A4 inhibitorNon-inhibitor0.8333
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8165
Ames testNon AMES toxic0.8311
CarcinogenicityNon-carcinogens0.659
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9282 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9987
hERG inhibition (predictor II)Non-inhibitor0.9207
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,4-benzodiazepines
Alternative Parents
Alpha amino acids and derivatives / Benzene and substituted derivatives / Aryl chlorides / 1,3-dicarbonyl compounds / Secondary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Monocarboxylic acids and derivatives / Carboxylic acids
show 5 more
Substituents
1,4-benzodiazepine / Alpha-amino acid or derivatives / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / 1,3-dicarbonyl compound / Carboxamide group / Ketimine / Lactam
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
1,4-benzodiazepinone (CHEBI:3761)

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Cholesterol binding
Specific Function
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in l...
Gene Name
TSPO
Uniprot ID
P30536
Uniprot Name
Translocator protein
Molecular Weight
18827.81 Da
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:8787774]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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:10668858]
  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:11251565]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37