Clorazepic acid

Identification

Summary

Clorazepic acid is a benzodiazepine used to treat anxiety, partial seizures, and alcohol withdrawal.

Brand Names
Tranxene
Generic Name
Clorazepic acid
DrugBank Accession Number
DB00628
Background

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

Type
Small Molecule
Groups
Approved, Illicit
Structure
Thumb
Weight
Average: 314.723
Monoisotopic: 314.045819935
Chemical Formula
C16H11ClN2O3
Synonyms
  • 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzodiazepine-3-carboxylic acid
  • Chlorazepate
  • Clorazepate
  • Clorazepic acid
External IDs
  • 4306-CB FREE ACID
  • 4311 CB
  • Abbott 35616
  • AH 3232
  • CB 4306
  • Ro 6-6616
  • TR 19119

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.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
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.

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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

Adverse Effects
Adverseeffects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Clorazepic acid is combined with 1,2-Benzodiazepine.
AbacavirClorazepic acid may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Clorazepic acid can be increased when it is combined with Abametapir.
AbirateroneThe metabolism of Clorazepic acid can be decreased when combined with Abiraterone.
AceclofenacAceclofenac may decrease the excretion rate of Clorazepic acid which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Clorazepic acid which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Clorazepic acid which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Clorazepic acid is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Clorazepic acid is combined with Acetophenazine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Clorazepic acid which could result in a higher serum level.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Take with or without food. The absorption is unaffected by food.

Products

Products2
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Product Ingredients
IngredientUNIICASInChI Key
Clorazepate dipotassium63FN7G03XY57109-90-7QCHSEDTUUKDTIG-UHFFFAOYSA-L
Product Images
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)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ClorazepateCapsule7.5 mgOralAa Pharma Inc1990-12-31Not applicableCanada flag
ClorazepateCapsule3.75 mgOralAa Pharma Inc1990-12-31Not applicableCanada flag
ClorazepateCapsule15 mgOralAa Pharma Inc1990-12-31Not applicableCanada flag
Clorazepate Dipotassium T-TabTablet7.5 mg/1OralAbbvie1972-06-232018-04-30US flag
Tranxene Cap 15mgCapsule15 mgOralAbbott1973-12-312003-08-01Canada flag
Tranxene Cap 3.75mgCapsule3.75 mgOralAbbott1973-12-312003-08-01Canada flag
Tranxene Cap 7.5mgCapsule7.5 mg / capOralAbbott1976-12-312003-08-01Canada flag
Tranxene T-TabTablet3.75 mg/1OralLundbeck Inc.1972-06-232013-04-12US flag
Tranxene T-TabTablet15 mg/1OralRECORDATI RARE DISEASES, INC.1972-06-232013-02-02US flag
Tranxene T-TabTablet15 mg/1OralLundbeck Inc.1972-06-232013-04-12US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Clorazepate DipotassiumTablet3.75 mg/1OralAmerincan Health Packaging2014-07-312017-05-31US flag51672 4042 02 nlmimage10 d6156b1b
Clorazepate DipotassiumTablet15 mg/1OralAurolife Pharma, LLC1987-07-17Not applicableUS flag
Clorazepate DipotassiumTablet3.75 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2000-04-27Not applicableUS flag51672 404220180907 15195 1hq1g48
Clorazepate DipotassiumTablet7.5 mg/1OralMylan Pharmaceuticals Inc.1987-07-17Not applicableUS flag
Clorazepate DipotassiumTablet3.75 mg/1OralRebel Distributors2000-04-27Not applicableUS flag21695 043320210315 21055 1n2wn6n
Clorazepate DipotassiumTablet7.5 mg/1OralContract Pharmacy Services Pa2011-03-29Not applicableUS flag
Clorazepate DipotassiumTablet15 mg/1Oralbryant ranch prepack2000-04-272010-09-01US flag63629 385920180907 15195 c3x3ck
Clorazepate DipotassiumTablet3.75 mg/1OralPhysicians Total Care, Inc.1996-05-242015-03-31US flag
Clorazepate dipotassiumTablet7.5 mg/1OralContract Pharmacy Services Pa2017-09-28Not applicableUS flag
Clorazepate DipotassiumTablet15 mg/1OralREMEDYREPACK INC.2016-07-152018-05-10US flag

Categories

ATC Codes
N05BA05 — Potassium clorazepate
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,3-dicarbonyl compound / 1,4-benzodiazepine / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
1,4-benzodiazepinone (CHEBI:3761)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
D51WO0G0L4
CAS number
23887-31-2
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

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. [Article]
  2. McElhatton PR: The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994 Nov-Dec;8(6):461-75. [Article]
  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. [Article]
Human Metabolome Database
HMDB0014766
KEGG Drug
D00694
KEGG Compound
C06921
PubChem Compound
2809
PubChem Substance
46506595
ChemSpider
2707
RxNav
235408
ChEBI
3761
ChEMBL
CHEMBL1213252
Therapeutic Targets Database
DAP000240
PharmGKB
PA164749297
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clorazepate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedPreventionDepression1
4Unknown StatusTreatmentCutaneous T Cell Lymphomas (CTCL) / Mycosis Fungoides (MF)1
3RecruitingTreatmentHeadache / Migraine / Migraine With Aura / Migraine Without Aura1
Not AvailableCompletedNot AvailableHealthy Subjects (HS)1

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
CapsuleOral
CapsuleOral3.75 mg
CapsuleOral7.5 mg
TabletOral15 mg/1
TabletOral3.75 mg/1
TabletOral7.5 mg/1
CapsuleOral10 MG
CapsuleOral15 MG
CapsuleOral5 MG
CapsuleOral7.5 mg / cap
CapsuleOral20 mg
Tablet, film coatedOral20 mg
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

Targets

Drugtargets2
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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
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. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
  2. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
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. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
  2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 26, 2021 21:40