CHLORZOXAZONE

First approved in 1958

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H4ClNO2
Molecular Weight	169.5654
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc2c(cc1Cl)nc(O)o2

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	169.5654
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 7 Target ID: CHEMBL4305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10712246	Activator 560

Conditions

Condition	Modality	Targets	Highest Phase	Product
Muscle spasm 21 Sources: http://www.rxlist.com/chlorzoxazone-drug/indications-dosage.htm	Primary		Approved 4033	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 882

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 332 CYP1A2 526 CYP1A1 179

Drug as victim

Target	Modality	Activity
CYP2E1 332	substrate 1689 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	major
CYP1A1 179	substrate 1689 Sources: https://link.springer.com/article/10.1007/s00228-018-2481-x Page: 1.0	minor
CYP1A2 526	substrate 1689 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	minor
CYP3A4 882	substrate 1689 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
EBIO, an agent causing maintained epithelial chloride secretion by co-ordinate actions at both apical and basolateral membranes.	2001	11845318
Chlorzoxazone: a probe drug the metabolism of which can be used to monitor one-point blood sampling in the carbon tetrachloride-intoxicated rat.	2001 Aug	11727787
Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components.	2001 Dec 15	11701226
Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes.	2001 Feb	11159803
Characterization of xenobiotic-metabolizing cytochrome P450 (CYP) forms in ringed and grey seals from the Baltic Sea and reference sites.	2001 Jan	11166678
One hundred percent online identity check of pharmaceutical products by near-infrared spectroscopy on the packaging line.	2001 Jan	11154898
Synthetic chloride channel restores glutathione secretion in cystic fibrosis airway epithelia.	2001 Jul	11404241
Spectrofluorometric determination of ibuprofen in pharmaceutical formulations.	2001 Jun	11377049
Genetic and dietary factors affecting human metabolism of 1,3-butadiene.	2001 Jun 1	11397404
Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.	2001 Mar	11465391
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
Toxicity and effects of 2,6-di-tert-butyl-4-methylphenyl N-methylcarbamate (terbutol) on hepatic cytochrome P450 in F344 rats.	2001 Nov	11760817
In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9).	2001 Nov	11736863
Assessment of cytochrome P450 activity by a five-drug cocktail approach.	2001 Nov	11719732
The effect of endotoxin on hepatocyte nuclear factor 1 nuclear protein binding: potential implications on CYP2E1 expression in the rat.	2001 Oct	11697544
Effect of chronic disulfiram administration on the activities of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and N-acetyltransferase in healthy human subjects.	2002 Feb	11851639
Dynamics of cytochrome P4502E1 activity in man: induction by ethanol and disappearance during withdrawal phase.	2002 Jan	11804663
Cytochrome P450 enzymes contributing to demethylation of maprotiline in man.	2002 Mar	12071336
The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes.	2002 Mar	11854157
Inhibition of cytochromes P450 by antifungal imidazole derivatives.	2002 Mar	11854151
Plasma levels of TNF-alpha and IL-6 are inversely related to cytochrome P450-dependent drug metabolism in patients with congestive heart failure.	2002 Oct	12411982
Cytochrome P4502E1 phenotyping by the measurement of the chlorzoxazone metabolic ratio: assessment of its usefulness in workers exposed to styrene.	2002 Sep	12172891
Kinetic study of alkaline induced hydrolysis of the skeletal muscle relaxant chlorzoxazone using ratio spectra first derivative spectrophotometry.	2003 Apr	12727544
The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine.	2003 Apr	12690492
Lipopolysaccharide-mediated modulation of cytochromes P450 in Stat1 null mice.	2003 Apr	12642464
Construction and assessment of models of CYP2E1: predictions of metabolism from docking, molecular dynamics, and density functional theoretical calculations.	2003 Apr 24	12699383
Phorbol ester induces CYP2E1 in astrocytes, through a protein kinase C- and tyrosine kinase-dependent mechanism.	2003 Aug	12887687
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
Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF.	2003 Aug	12711595
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
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
Effects of acute renal failure on the pharmacokinetics of chlorzoxazone in rats.	2003 Jun	12756212
Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.	2003 Jun 6	12757833
Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects.	2003 Mar	12621391
Pharmacokinetics of intravenous chlorzoxazone in rats with dehydration and rehydration: effects of food intakes.	2003 Mar	12619050
Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis.	2003 Mar	12601351
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 `Fri Jun 25 20:58:15 UTC 2021` Edited by `admin` on `Fri Jun 25 20:58:15 UTC 2021`
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 [USP]

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

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 [WHO-DD]

Common Name

English

CHLORZOXAZONE [USP MONOGRAPH]

Common Name

English

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

Systematic Name

English

Classification Tree Code System Code

LIVERTOX

200