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Identification
Name Chlorzoxazone
Accession Number DB00356 (APRD00308)
Type small molecule
Groups approved
Description

A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Chloroxazone
  • Chlorzoxane
  • Chlorzoxazon
Brand names
  • Biomioran
  • Escoflex
  • EZE-DS
  • Flexazone
  • Mioran
  • Miotran
  • Myoflexin
  • Myoflexine
  • Neoflex
  • Paraflex
  • Parafon Forte Dsc
  • Pathorysin
  • Relaxazone
  • Remular
  • Remular-S
  • Solaxin
  • Strifon Forte Dsc
  • Usaf Ma-10
Brand name mixtures
  • Acetazone Forte (Acetaminophen + Chlorzoxazone)
  • Acetazone Forte C8 (Acetaminophen + Chlorzoxazone + Codeine Phosphate)
  • Back-Aid Forte - Tab (Acetaminophen + Chlorzoxazone)
  • Extra Strength Tylenol Aches and Strains (Acetaminophen + Chlorzoxazone)
  • Gin Pain Pills - Tab (Acetaminophen + Chlorzoxazone)
  • Gin Pain Pills- Chlorzoxazone & Acetamin.Tab (Acetaminophen + Chlorzoxazone)
  • Parafon Forte (Acetaminophen + Chlorzoxazone)
  • Parafon Forte C8 W Codeine Tab (Acetaminophen + Chlorzoxazone + Codeine Phosphate)
  • Parafon Forte Tablets (Acetaminophen + Chlorzoxazone)
Categories
  • Muscle Relaxants, Central
CAS number 95-25-0
Weight Average: 169.565
Monoisotopic: 168.993056084
Chemical Formula C7H4ClNO2
InChI Key InChIKey=TZFWDZFKRBELIQ-UHFFFAOYSA-N
InChI
InChI=1S/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)
Plain Text
IUPAC Name
5-chloro-2,3-dihydro-1,3-benzoxazol-2-one
SMILES
ClC1=CC2=C(OC(=O)N2)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzoxazoles
Substructures
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Benzoxazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Oxazoles
Pharmacology
Indication For the relief of discomfort associated with acute painful musculoskeletal conditions.
Pharmacodynamics Chlorzoxazone, a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Chlorzoxazone is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis. Chlorzoxazone is also a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles.
Mechanism of action Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm
Absorption Not Available
Volume of distribution Not Available
Protein binding 13-18%
Metabolism

Chlorzoxazone is rapidly metabolized in the liver and is excreted in the urine, primarily in a conjugated form as the glucuronide.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2E1 6-hydroxychlorzoxazone 6-hydroxylation 40 7.5
Route of elimination Chlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Half life Not Available
Clearance Not Available
Toxicity Oral, mouse: LD50 = 440 mg/kg; Oral, rat: LD50 = 763 mg/kg; Symptoms of overdose include diarrhea, dizziness, drowsiness, headache, light-headedness, nausea, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Actavis totowa llc
  • Barr laboratories inc
  • Mikart inc
  • Mutual pharmaceutical co inc
  • Ohm laboratories inc
  • Par pharmaceutical inc
  • Pioneer pharmaceuticals inc
  • Sandoz inc
  • Watson laboratories inc
  • Ortho mcneil pharmaceutical inc
  • Ortho mcneil janssen pharmaceuticals inc
  • Ferndale laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Parafon forte dsc 500 mg caplet 2.65 USD caplet
Chlorzoxazone 500 mg tablet 0.87 USD tablet
Chlorzoxazone 250 mg tablet 0.18 USD tablet
Patents Not Available
Properties
State solid
Melting point 191.5 oC
Experimental Properties
Property Value Source
water solubility 1000 mg/L PhysProp
logP 1.6 PhysProp
Predicted Properties
Property Value Source
water solubility 2.96e+00 g/l ALOGPS
logP 2.09 ALOGPS
logP 1.94 ChemAxon Molconvert
logS -1.76 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 38.33 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 41.07 ChemAxon Molconvert
polarizability 14.94 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Dong DL, Luan Y, Feng TM, Fan CL, Yue P, Sun ZJ, Gu RM, Yang BF: Chlorzoxazone inhibits contraction of rat thoracic aorta. Eur J Pharmacol. 2006 Sep 18;545(2-3):161-6. Epub 2006 Jun 29. Pubmed
  2. Park JY, Kim KA, Park PW, Ha JM: Effect of high-dose aspirin on CYP2E1 activity in healthy subjects measured using chlorzoxazone as a probe. J Clin Pharmacol. 2006 Jan;46(1):109-14. Pubmed
  3. Wan J, Ernstgard L, Song BJ, Shoaf SE: Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats. J Pharm Pharmacol. 2006 Jan;58(1):51-61. Pubmed
External Links
Resource Link
KEGG Drug D00771 Link_out
KEGG Compound C07931 Link_out
PubChem Compound 2733 Link_out
PubChem Substance 46507755 Link_out
ChemSpider 2632 Link_out
ChEBI 3655 Link_out
ChEMBL 3655 Link_out
Therapeutic Targets Database DAP000952 Link_out
PharmGKB PA448971 Link_out
HET CLW Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/chlorzox.htm Link_out
Drugs.com http://www.drugs.com/cdi/chlorzoxazone.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/par1317.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Chlorzoxazone Link_out
ATC Codes
  • M03BB03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (61.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Targets

1. Calcium-activated potassium channel subunit alpha 1

Pharmacological action: yes
Actions: inducer

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)

Organism class: human
UniProt ID: Q12791 Link_out
Gene: KCNMA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Dong DL, Luan Y, Feng TM, Fan CL, Yue P, Sun ZJ, Gu RM, Yang BF: Chlorzoxazone inhibits contraction of rat thoracic aorta. Eur J Pharmacol. 2006 Sep 18;545(2-3):161-6. Epub 2006 Jun 29. Pubmed
  4. Alvina K, Khodakhah K: KCa channels as therapeutic targets in episodic ataxia type-2. J Neurosci. 2010 May 26;30(21):7249-57. Pubmed
  5. Syme CA, Gerlach AC, Singh AK, Devor DC: Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels. Am J Physiol Cell Physiol. 2000 Mar;278(3):C570-81. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: substrate, inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. Pubmed
  3. 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
  4. Yasar U, Forslund-Bergengren C, Tybring G, Dorado P, Llerena A, Sjoqvist F, Eliasson E, Dahl ML: Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther. 2002 Jan;71(1):89-98. Pubmed

2. Cytochrome P450 1A1

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wiercinska P, Squires EJ: Chlorzoxazone metabolism by porcine cytochrome P450 enzymes and the effect of cytochrome b5. Drug Metab Dispos. 2010 May;38(5):857-62. Epub 2010 Feb 17. Pubmed
  2. Warrington JS, Court MH, Greenblatt DJ, von Moltke LL: Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats. J Pharm Pharmacol. 2004 Jun;56(6):819-25. Pubmed

3. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Cytochrome P450 2A6

Actions: substrate

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on August 03, 2011 08:25

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.