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 10 Target ID: CHEMBL4305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10712246	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Muscle spasm 40 Sources: http://www.rxlist.com/chlorzoxazone-drug/indications-dosage.htm	Primary		Approved 8429	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 1988

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 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 667 CYP1A2 1054 CYP1A1 349

Drug as victim

Target	Modality	Activity
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	major
CYP1A1 349	substrate 3367 Sources: https://link.springer.com/article/10.1007/s00228-018-2481-x Page: 1.0	minor
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	minor
CYP3A4 1737	substrate 3367 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
Mechanism of aerobic transformation of carbon tetrachloride by poplar cells.	2002	12688582
Fondaparinux sodium is not metabolised in mammalian liver fractions and does not inhibit cytochrome P450-mediated metabolism of concomitant drugs.	2002	12383041
Effects of cysteine on the pharmacokinetics of intravenous chlorzoxazone in rats with protein-calorie malnutrition.	2002 Apr	12173547
Validated HPLC method for determination of chlorzoxazone in human serum and its application in a clinical pharmacokinetic study.	2002 Dec	12561241
Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions.	2002 Dec	12433797
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
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
Monolithic silica rod liquid chromatography with ultraviolet or fluorescence detection for metabolite analysis of cytochrome P450 marker reactions.	2002 Nov 25	12401345
Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: crystallographic and computational analyses of inhibitor potency.	2002 Nov 26	12437348
Cytochrome P450 2E1 expression induces hepatocyte resistance to cell death from oxidative stress.	2002 Oct	12470497
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
Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption.	2002 Oct	12351530
Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes.	2002 Oct 1	12234619
Watercress has no Importance for the elimination of ethanol by CYP2E1 inhibition.	2002 Sep	12427108
Cytochrome P450 2E1 and 3A activities do not differ between Mexicans and European Americans.	2002 Sep	12235449
Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans.	2002 Sep	12235448
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
Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis.	2003 Apr	12668988
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
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
Diabetes mellitus increases the in vivo activity of cytochrome P450 2E1 in humans.	2003 Jan	12534643
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
Unexpected down-regulation of the hIK1 Ca2+-activated K+ channel by its opener 1-ethyl-2-benzimidazolinone in HaCaT keratinocytes. Inverse effects on cell growth and proliferation.	2003 Jan 31	12421833
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
Metabolism of chloroform in the human liver and identification of the competent P450s.	2003 Mar	12584152
Cytochrome P450 expression and testosterone metabolism in the liver of deer.	2003 May 1	12679052
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
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 16 05:13:25 GMT 2023` Edited by `admin` on `Sat Dec 16 05:13:25 GMT 2023`
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