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Identification
NameChlorzoxazone
Accession NumberDB00356  (APRD00308)
TypeSmall Molecule
GroupsApproved
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
Synonyms
SynonymLanguageCode
2-hydroxy-5-chlorobenzoxazoleNot AvailableNot Available
5-chloro-2-BenzoxazolinoneNot AvailableNot Available
5-chloro-2-BenzoxazololNot AvailableNot Available
5-chloro-2-BenzoxazoloneNot AvailableNot Available
5-chloro-2-HydroxybenzoxazoleNot AvailableNot Available
5-chloro-2(3H)-benzoxazoloneNot AvailableNot Available
5-chloro-3H-benzooxazol-2-oneNot AvailableIUPAC
5-ChlorobenzoxazolidoneNot AvailableNot Available
5-chlorobenzoxazolin-2-oneNot AvailableNot Available
ChlorzoxaneNot AvailableNot Available
ChlorzoxazonGermanINN
ChlorzoxazonaNot AvailableNot Available
ChlorzoxazoneNot AvailableBAN, DCF, USP 34
ChlorzoxazonumLatinINN
ClorzoxazonaSpanishINN
ClorzoxazoneNot AvailableDCIT
SaltsNot Available
Brand names
NameCompany
LorzoneNot Available
MyoflexinZentiva
ParaflexBioPhausia
Parafon ForteJanssen
Parafon Forte DSCJanssen
RelaxazoneNot Available
RemularNot Available
Remular-SNot Available
SolaxinEisai
Strifon Forte DSCNot Available
Brand mixtures
Brand NameIngredients
Acetazone ForteAcetaminophen + Chlorzoxazone
Acetazone Forte C8Acetaminophen + Chlorzoxazone + Codeine Phosphate
Back-Aid ForteAcetaminophen + Chlorzoxazone
Extra Strength Tylenol Aches and StrainsAcetaminophen + Chlorzoxazone
Gin Pain PillsAcetaminophen + Chlorzoxazone
MuscolAcetaminophen + Chlorzoxazone
Parafon ForteAcetaminophen + Chlorzoxazone
Parafon Forte C8 with CodeineAcetaminophen + Chlorzoxazone + Codeine Phosphate
Categories
CAS number95-25-0
WeightAverage: 169.565
Monoisotopic: 168.993056084
Chemical FormulaC7H4ClNO2
InChI KeyTZFWDZFKRBELIQ-UHFFFAOYSA-N
InChI
InChI=1S/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)
IUPAC Name
5-chloro-2,3-dihydro-1,3-benzoxazol-2-one
SMILES
ClC1=CC2=C(OC(=O)N2)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzoxazoles
SubclassBenzoxazolones
Direct parentBenzoxazolones
Alternative parentsChlorobenzenes; Aryl Chlorides; Oxazoles; Polyamines; Organochlorides
Substituentschlorobenzene; aryl halide; benzene; aryl chloride; oxazole; azole; polyamine; organochloride; organohalogen; organonitrogen compound
Classification descriptionThis compound belongs to the benzoxazolones. These are organic compounds containing a benzene fused to an oxazole ring (a five-member aliphatic ring with three carbon atoms, one oxygen atom, and one nitrogen atom) beraing a ketone group.
Pharmacology
IndicationFor the relief of discomfort associated with acute painful musculoskeletal conditions.
PharmacodynamicsChlorzoxazone, 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 actionChlorzoxazone 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
AbsorptionNot Available
Volume of distributionNot Available
Protein binding13-18%
Metabolism

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

SubstrateEnzymesProduct
Chlorzoxazone
6-hydroxychlorzoxazoneDetails
Route of eliminationChlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Half lifeNot Available
ClearanceNot Available
ToxicityOral, 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.991
Caco-2 permeable + 0.5
P-glycoprotein substrate Non-substrate 0.8733
P-glycoprotein inhibitor I Non-inhibitor 0.9784
P-glycoprotein inhibitor II Non-inhibitor 0.9263
Renal organic cation transporter Non-inhibitor 0.9001
CYP450 2C9 substrate Non-substrate 0.8243
CYP450 2D6 substrate Substrate 0.6471
CYP450 3A4 substrate Non-substrate 0.5372
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9539
CYP450 2D6 substrate Non-inhibitor 0.9338
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9522
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8682
Ames test Non AMES toxic 0.7957
Carcinogenicity Non-carcinogens 0.9467
Biodegradation Not ready biodegradable 0.9655
Rat acute toxicity 2.2388 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8675
hERG inhibition (predictor II) Non-inhibitor 0.9659
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
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Parafon forte dsc 500 mg caplet2.65USDcaplet
Chlorzoxazone 500 mg tablet0.87USDtablet
Chlorzoxazone 250 mg tablet0.18USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point191-191.5Marsh, D.F.; US. Patent 2,895,877; July 21, 1959; assigned to McNeil Laboratories, Inc.
water solubility1000 mg/LNot Available
logP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.96ALOGPS
logP2.09ALOGPS
logP1.94ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)9.39ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.33 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity41.07 m3·mol-1ChemAxon
Polarizability14.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Marsh, D.F.; US. Patent 2,895,877; July 21, 1959; assigned to McNeil Laboratories, Inc.

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
ResourceLink
KEGG DrugD00771
KEGG CompoundC07931
PubChem Compound2733
PubChem Substance46507755
ChemSpider2632
ChEBI3655
ChEMBLCHEMBL1371
Therapeutic Targets DatabaseDAP000952
PharmGKBPA448971
IUPHAR2322
Guide to Pharmacology2322
HETCLW
RxListhttp://www.rxlist.com/cgi/generic2/chlorzox.htm
Drugs.comhttp://www.drugs.com/cdi/chlorzoxazone.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/par1317.shtml
WikipediaChlorzoxazone
ATC CodesM03BB03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(61.8 KB)
Interactions
Drug Interactions
Drug
DisulfiramDisulfiram may increase the serum level of chlorzoxazone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of chlorzoxazone if diltiazem is initiated, discontinued or dose changed.
TriprolidineThe CNS depressants, Triprolidine and Chlorzoxazone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

Targets

1. Calcium-activated potassium channel subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Calcium-activated potassium channel subunit alpha-1 Q12791 Details

References:

  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. Alvina K, Khodakhah K: KCa channels as therapeutic targets in episodic ataxia type-2. J Neurosci. 2010 May 26;30(21):7249-57. Pubmed
  3. 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

Enzymes

1. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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. Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. Pubmed
  4. Ernstgard L, Warholm M, Johanson G: Robustness of chlorzoxazone as an in vivo measure of cytochrome P450 2E1 activity. Br J Clin Pharmacol. 2004 Aug;58(2):190-200. Pubmed

2. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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
  2. Yang TJ, Sai Y, Krausz KW, Gonzalez FJ, Gelboin HV: Inhibitory monoclonal antibodies to human cytochrome P450 1A2: analysis of phenacetin O-deethylation in human liver. Pharmacogenetics. 1998 Oct;8(5):375-82. Pubmed

4. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

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
  2. Shimada T, Tsumura F, Yamazaki H: Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Nov;27(11):1274-80. Pubmed

5. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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
  2. Gorski JC, Jones DR, Wrighton SA, Hall SD: Contribution of human CYP3A subfamily members to the 6-hydroxylation of chlorzoxazone. Xenobiotica. 1997 Mar;27(3):243-56. Pubmed

6. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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
  2. Shimada T, Tsumura F, Yamazaki H: Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Nov;27(11):1274-80. Pubmed
  3. Gorski JC, Jones DR, Wrighton SA, Hall SD: Contribution of human CYP3A subfamily members to the 6-hydroxylation of chlorzoxazone. Xenobiotica. 1997 Mar;27(3):243-56. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 04, 2014 12:03