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
Structure for Clorazepic acid (DB00628)
- 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.
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with 1,2-Benzodiazepine. Abacavir Clorazepic acid may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Clorazepic acid can be increased when it is combined with Abametapir. Abiraterone The metabolism of Clorazepic acid can be decreased when combined with Abiraterone. Aceclofenac Aceclofenac may decrease the excretion rate of Clorazepic acid which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Clorazepic acid which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Clorazepic acid which could result in a higher serum level. Acetazolamide The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Acetazolamide. Acetophenazine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Acetophenazine. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Clorazepic acid which could result in a higher serum level. 
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- Avoid alcohol.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Clorazepate dipotassium 63FN7G03XY 57109-90-7 QCHSEDTUUKDTIG-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
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clorazepate Capsule 7.5 mg Oral Aa Pharma Inc 1990-12-31 Not applicable Canada 
Clorazepate Capsule 3.75 mg Oral Aa Pharma Inc 1990-12-31 Not applicable Canada Clorazepate Capsule 15 mg Oral Aa Pharma Inc 1990-12-31 Not applicable Canada Clorazepate Dipotassium T-Tab Tablet 7.5 mg/1 Oral Abbvie 1972-06-23 2018-04-30 US 
Tranxene Cap 15mg Capsule 15 mg Oral Abbott 1973-12-31 2003-08-01 Canada Tranxene Cap 3.75mg Capsule 3.75 mg Oral Abbott 1973-12-31 2003-08-01 Canada Tranxene Cap 7.5mg Capsule 7.5 mg / cap Oral Abbott 1976-12-31 2003-08-01 Canada Tranxene T-Tab Tablet 3.75 mg/1 Oral Lundbeck Inc. 1972-06-23 2013-04-12 US Tranxene T-Tab Tablet 15 mg/1 Oral RECORDATI RARE DISEASES, INC. 1972-06-23 2013-02-02 US Tranxene T-Tab Tablet 15 mg/1 Oral Lundbeck Inc. 1972-06-23 2013-04-12 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clorazepate Dipotassium Tablet 3.75 mg/1 Oral Amerincan Health Packaging 2014-07-31 2017-05-31 US 
Clorazepate Dipotassium Tablet 15 mg/1 Oral Aurolife Pharma, LLC 1987-07-17 Not applicable US Clorazepate Dipotassium Tablet 3.75 mg/1 Oral Taro Pharmaceuticals U.S.A., Inc. 2000-04-27 Not applicable US 
Clorazepate Dipotassium Tablet 7.5 mg/1 Oral Mylan Pharmaceuticals Inc. 1987-07-17 Not applicable US Clorazepate Dipotassium Tablet 3.75 mg/1 Oral Rebel Distributors 2000-04-27 Not applicable US 
Clorazepate Dipotassium Tablet 7.5 mg/1 Oral Contract Pharmacy Services Pa 2011-03-29 Not applicable US Clorazepate Dipotassium Tablet 15 mg/1 Oral bryant ranch prepack 2000-04-27 2010-09-01 US 
Clorazepate Dipotassium Tablet 3.75 mg/1 Oral Physicians Total Care, Inc. 1996-05-24 2015-03-31 US Clorazepate dipotassium Tablet 7.5 mg/1 Oral Contract Pharmacy Services Pa 2017-09-28 Not applicable US Clorazepate Dipotassium Tablet 15 mg/1 Oral REMEDYREPACK INC. 2016-07-15 2018-05-10 US
Categories
- ATC Codes
- N05BA05 — Potassium clorazepate
- Drug Categories
- Anti-Anxiety Agents
- Anticonvulsants
- Benzazepines
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Modulators
- Heterocyclic Compounds, Fused-Ring
- Nervous System
- Neurotransmitter Agents
- Psycholeptics
- Psychotropic Drugs
- Tranquilizing Agents
- 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
- 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]
- McElhatton PR: The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994 Nov-Dec;8(6):461-75. [Article]
- 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]
- External Links
- Human Metabolome Database
- HMDB0014766
- KEGG Drug
- D00694
- KEGG Compound
- C06921
- PubChem Compound
- 2809
- PubChem Substance
- 46506595
- ChemSpider
- 2707
- 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
Phase Status Purpose Conditions Count 4 Terminated Prevention Depression 1 4 Unknown Status Treatment Cutaneous T Cell Lymphomas (CTCL) / Mycosis Fungoides (MF) 1 3 Recruiting Treatment Headache / Migraine / Migraine With Aura / Migraine Without Aura 1 Not Available Completed Not Available Healthy 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
Form Route Strength Capsule Oral Capsule Oral 3.75 mg Capsule Oral 7.5 mg Tablet Oral 15 mg/1 Tablet Oral 3.75 mg/1 Tablet Oral 7.5 mg/1 Capsule Oral 10 MG Capsule Oral 15 MG Capsule Oral 5 MG Capsule Oral 7.5 mg / cap Capsule Oral 20 mg Tablet, film coated Oral 20 mg - Prices
Unit description Cost Unit Tranxene t-tablet 15 mg 5.41USD tablet Tranxene-T 15 mg tablet 5.08USD tablet Tranxene t-tablet 7.5 mg 3.99USD tablet Tranxene-T 7.5 mg tablet 3.6USD tablet Tranxene t-tablet 3.75 mg 3.21USD tablet Tranxene-T 3.75 mg tablet 3.04USD tablet Clorazepate 15 mg tablet 2.17USD tablet Clorazepate Dipotassium 15 mg tablet 1.27USD tablet Clorazepate Dipotassium 7.5 mg tablet 0.93USD tablet Clorazepate 7.5 mg tablet 0.79USD tablet Clorazepate Dipotassium 3.75 mg tablet 0.76USD tablet Clorazepate 3.75 mg tablet 0.73USD tablet Apo-Clorazepate 15 mg Capsule 0.4USD capsule Apo-Clorazepate 7.5 mg Capsule 0.2USD capsule Apo-Clorazepate 3.75 mg Capsule 0.15USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Very soluble Not Available logP 3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0248 mg/mL ALOGPS logP 2.68 ALOGPS logP 3.21 ChemAxon logS -4.1 ALOGPS pKa (Strongest Acidic) 3.32 ChemAxon pKa (Strongest Basic) -0.64 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 78.76 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 82.68 m3·mol-1 ChemAxon Polarizability 30.63 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - 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 inhibitor Non-inhibitor 0.756 CYP450 2D6 inhibitor Non-inhibitor 0.819 CYP450 2C19 inhibitor Non-inhibitor 0.7451 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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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
- 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]
- 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
- 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]
- 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
- 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]
- 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