CHLORZOXAZONE

First approved in 1958

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H4ClNO2
Molecular Weight	169.565
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC=C2OC(=O)NC2=C1

InChI

InChIKey=TZFWDZFKRBELIQ-UHFFFAOYSA-N

InChI=1S/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)

HIDE SMILES / InChI

Molecular Formula	C7H4ClNO2
Molecular Weight	169.565
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.rxlist.com/chlorzoxazone-drug.htm
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68002753

Chlorzoxazone is 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 where it inhibits multisynaptic reflex arcs 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. Chlorzoxazone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone does not directly relax tense skeletal muscles in man.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Intermediate conductance calcium-activated potassium channel protein 4 8 Target ID: CHEMBL4305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10712246	Activator 1404

Conditions

Condition	Modality	Targets	Highest Phase	Product
Muscle spasm 40 Sources: http://www.rxlist.com/chlorzoxazone-drug/indications-dosage.htm	Primary		Approved 8307	CHLORZOXAZONE Approved Use INDICATIONS & USAGE SECTION Chlorzoxazone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone does not directly relax tense skeletal muscles in man. Launch Date 5.7870719E11

C_max

Value	Dose	Co-administered	Analyte	Population
36.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6631711/	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: QUERCETIN	QUERCETIN	CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.45 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
12.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: QUERCETIN	QUERCETIN	6-HYDROXYCHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		6-HYDROXYCHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
4084 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6631711/	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
16.69 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: QUERCETIN	QUERCETIN	CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.86 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
43.5 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
15.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
32.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.64 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: QUERCETIN	QUERCETIN	6-HYDROXYCHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.95 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		6-HYDROXYCHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6631711/	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: ACETAMINOPHEN	ACETAMINOPHEN	CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: QUERCETIN	QUERCETIN	CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28983678/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Analyte	Population
3.9% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	CHLORZOXAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12534643/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	CHLORZOXAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 633 CYP1A2 1013 CYP1A1 344

Drug as victim

Target	Modality	Activity
CYP2E1 633	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	major
CYP1A1 344	substrate 3264 Sources: https://link.springer.com/article/10.1007/s00228-018-2481-x Page: 1.0	minor
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	minor
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	minor

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3655	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3655
ChemicalBook	CB0392987	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0392987
MolPort	MolPort-001-759-947	https://www.molport.com/shop/molecule-link/MolPort-001-759-947
MolPort	MolPort-006-110-468	https://www.molport.com/shop/molecule-link/MolPort-006-110-468
Selleck Chemicals	chlorzoxazone	http://www.selleckchem.com/products/chlorzoxazone.html
ZINC	ZINC000084843283	http://zinc15.docking.org/substances/ZINC000084843283
eMolecules	536115	https://www.emolecules.com/cgi-bin/more?vid=536115
eMolecules	901630	https://www.emolecules.com/cgi-bin/more?vid=901630

PubMed

Title	Date	PubMed
[Rhabdomyolysis and cholestatic hepatitis under treatment with simvastatin and chlorzoxazone].	1999 Apr 3	10322565
CYP2E1-dependent benzene toxicity: the role of extrahepatic benzene metabolism.	1999 Jun-Jul	10463382
Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels.	2000 Mar	10712246
EBIO, an agent causing maintained epithelial chloride secretion by co-ordinate actions at both apical and basolateral membranes.	2001	11845318
Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate.	2001 Aug	11454729
Genetic and dietary factors affecting human metabolism of 1,3-butadiene.	2001 Jun 1	11397404
Tissue-specific alterations in the 6-hydroxylation of chlorzoxazone following traumatic brain injury in the rat.	2001 Mar	11181498
In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine), and its nonamine analog, cyclopropylbenzene.	2001 Mar	11181487
Mitochondrial dysfunction by gamma-irradiation accompanies the induction of cytochrome P450 2E1 (CYP2E1) in rat liver.	2001 Mar 21	11295257
Metabolism of vanoxerine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, by human cytochrome P450 enzymes.	2001 Sep	11502731
Mechanism of aerobic transformation of carbon tetrachloride by poplar cells.	2002	12688582
Validated HPLC method for determination of chlorzoxazone in human serum and its application in a clinical pharmacokinetic study.	2002 Dec	12561241
Effect of chronic disulfiram administration on the activities of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and N-acetyltransferase in healthy human subjects.	2002 Feb	11851639
Cytochrome P450 enzymes contributing to demethylation of maprotiline in man.	2002 Mar	12071336
Effects of flavonoids isolated from Scutellariae radix on cytochrome P-450 activities in human liver microsomes.	2002 Mar	11936218
The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes.	2002 Mar	11854157
Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat.	2002 Mar 1	11911841
[Simultaneous determination of three probe drugs by reversed-phase high performance liquid chromatography].	2002 Nov	12683003
Phenotype distribution and gender-related differences of CYP2E1 activity in a Chinese population.	2002 Nov	12487734
Cytochrome P450 2E1 expression induces hepatocyte resistance to cell death from oxidative stress.	2002 Oct	12470497
Lipopolysaccharide-mediated modulation of cytochromes P450 in Stat1 null mice.	2003 Apr	12642464
Effects of glucose on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.	2003 Aug	12884247
CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease.	2003 Aug	12883487
Rates of metabolism of chlorzoxazone, dextromethorphan, 7-ethoxycoumarin, imipramine, quinidine, testosterone and verapamil by fresh and cryopreserved rat liver slices, and some comparisons with microsomes.	2003 Aug	12849732
Simultaneous determination of aspirin and isosorbide 5-mononitrate in formulation by reversed phase high pressure liquid chromatography.	2003 Aug 21	12907257
Study of the fragmentation mechanism of protonated 6-hydroxychlorzoxazone: application in simultaneous analysis of CYP2E1 activity with major human cytochrome P450s.	2003 Feb 1	12585472
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
Determination of 6-hydroxychlorzoxazone and chlorzoxazone in porcine microsome samples.	2003 Jan 25	12504188
Stimulatory effects of chlorzoxazone, a centrally acting muscle relaxant, on large conductance calcium-activated potassium channels in pituitary GH3 cells.	2003 Jan 3	12480161
Maintenance of liver functions in rat hepatocytes cultured as spheroids in a rotating wall vessel.	2003 Jan-Feb	12892522
Differential inhibition of human cytochrome P450 enzymes by epsilon-viniferin, the dimer of resveratrol: comparison with resveratrol and polyphenols from alcoholized beverages.	2003 Jul 18	12818727
Diterpene quinone tanshinone IIA selectively inhibits mouse and human cytochrome p4501A2.	2003 Jun	12851037
Functional characterization of three human cytochrome p450 2E1 variants with amino acid substitutions.	2003 Jun	12851035
How useful is the "cocktail approach" for evaluating human hepatic drug metabolizing capacity using cytochrome P450 phenotyping probes in vivo?	2003 Jun	12795773
Metabolism of chloroform in the human liver and identification of the competent P450s.	2003 Mar	12584152
Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine metabolism.	2003 Nov	14586387
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor.	2003 Nov	14570767
GYKI-47261, a new AMPA [2-amino-3-(3-hydroxymethylisoxazole-4-yl)propionic acid] antagonist, is a CYP2E1 inducer.	2003 Nov	14570761
CYP2E1 regulation by benzene and other small organic chemicals in rat liver and peripheral lymphocytes.	2003 Sep 15	12919724
ATP release triggered by activation of the Ca2+-activated K+ channel in human airway Calu-3 cells.	2004 Mar	12947021

Patents

Sample Use Guides

In Vivo Use Guide

One tablet three or four times daily. If adequate response is not obtained with this dose, it may be increased to one and one-half tablets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

Route of Administration: Oral

In Vitro Use Guide

Chlorzoxazone did not affect the tension of the rat thoracic artery rings at rest, but relaxed the precontraction induced by 1 uM noradrenaline in an endothelium independent manner. Preincubation with chlorzoxazone also antagonized the contraction induced by 1 uM noradrenaline or 25 mM KCl.

Substance Class	Chemical Created by `admin` on `Sat Dec 17 18:02:21 UTC 2022` Edited by `admin` on `Sat Dec 17 18:02:21 UTC 2022`
Record UNII	H0DE420U8G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CHLORZOXAZONE

Official Name

English

CHLORZOXAZONE [MART.]

Common Name

English

chlorzoxazone [INN]

Common Name

English

Chlorzoxazone [WHO-DD]

Common Name

English

CHLORZOXAZONE [USP-RS]

Common Name

English

5-Chloro-2-benzoxazolinone

Systematic Name

English

STRIFON

Brand Name

English

CHLORZOXAZONE [JAN]

Common Name

English

CHLORZOXAZONE [USP IMPURITY]

Common Name

English

PARAFLEX

Brand Name

English

CHLORZOXAZONE [MI]

Common Name

English

CHLORZOXAZONE [ORANGE BOOK]

Common Name

English

PARAFON

Brand Name

English

CHLORZOXAZONE [VANDF]

Common Name

English

CHLORZOXAZONE [USP MONOGRAPH]

Common Name

English

2(3H)-BENZOXAZOLONE, 5-CHLORO-

Systematic Name

English

Classification Tree Code System Code

LIVERTOX

NBK548137