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 1410

Conditions

Condition	Modality	Targets	Highest Phase	Product
Muscle spasm 40 Sources: http://www.rxlist.com/chlorzoxazone-drug/indications-dosage.htm	Primary		Approved 8360	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 1709

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2E1 648 CYP1A2 1032 CYP1A1 348

Drug as victim

Target	Modality	Activity
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	major
CYP1A1 348	substrate 3326 Sources: https://link.springer.com/article/10.1007/s00228-018-2481-x Page: 1.0	minor
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25815637/ Page: 7.0	minor
CYP3A4 1709	substrate 3326 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
Metabolism of benzene in human liver microsomes: individual variations in relation to CYP2E1 expression.	1999 Feb	10207612
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
High-throughput cytochrome P450 (CYP) inhibition screening via a cassette probe-dosing strategy. VI. Simultaneous evaluation of inhibition potential of drugs on human hepatic isozymes CYP2A6, 3A4, 2C9, 2D6 and 2E1.	2001	11344532
Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes.	2001 Feb	11159803
Assessment of CFTR chloride channel openers in intact normal and cystic fibrosis murine epithelia.	2001 Feb	11159718
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
Genetic repeat polymorphism in the regulating region of CYP2E1: frequency and relationship with enzymatic activity in alcoholics.	2001 Jun	11410713
Identification of multiple constitutive and inducible hepatic cytochrome P450 enzymes in market weight swine.	2001 Jun	11353762
Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.	2001 Mar	11465391
Cytochrome P450 expression and related metabolism in human buccal mucosa.	2001 Mar	11238190
Cytochrome p450-dependent metabolism of trichloroethylene in rat kidney.	2001 Mar	11222868
Modulation of recombinant small-conductance Ca(2+)-activated K(+) channels by the muscle relaxant chlorzoxazone and structurally related compounds.	2001 Mar	11181893
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
A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6-hydroxylation and testosterone 6beta-hydroxylation.	2001 May 16	11336973
In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9).	2001 Nov	11736863
Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices.	2001 Nov	11703563
Low doses of nicotine and ethanol induce CYP2E1 and chlorzoxazone metabolism in rat liver.	2001 Nov	11602665
Mechanism of aerobic transformation of carbon tetrachloride by poplar cells.	2002	12688582
Effect of methacrylonitrile on cytochrome P-450 2E1 (CYP2E1) expression in male F344 rats.	2002 Apr 12	11939710
Validated HPLC method for determination of chlorzoxazone in human serum and its application in a clinical pharmacokinetic study.	2002 Dec	12561241
The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes.	2002 Mar	11854157
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
Cytochrome P450 2E1 and 3A activities do not differ between Mexicans and European Americans.	2002 Sep	12235449
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
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
Functional characterization of three human cytochrome p450 2E1 variants with amino acid substitutions.	2003 Jun	12851035
Cytochrome P450 expression and testosterone metabolism in the liver of deer.	2003 May 1	12679052
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 `Thu Jul 06 11:00:39 UTC 2023` Edited by `admin` on `Thu Jul 06 11:00:39 UTC 2023`
Record UNII	H0DE420U8G
Record Status	`Validated (UNII)`
Record Version

Download

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