QuickView for chlorzoxazone (compound)

Summary
General Info

PubChem

PubChem Compound 11052057

Name:	Chlorzoxazone
PubChem Compound ID:	11052057
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)
Molecular formula:	C₇H₄ClNO₂
Molecular weight:	168.566 g/mol

DrugBank

Identification

Name:	Chlorzoxazone
Name (isomeric):	DB00356
Drug Type:	small molecule
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)
Synonyms:	Chlorzoxane; Chloroxazone; Chlorzoxazon
Brand:	Mioran, Neoflex, Remular, Flexazone, Solaxin, EZE-DS, Escoflex, Pathorysin, Paraflex, Strifon Forte Dsc, Parafon Forte Dsc, Relaxazone, Usaf Ma-10, Remular-S, Biomioran, Myoflexin, Miotran, Myoflexine
Brand name mixture:	Acetazone Forte(Acetaminophen + Chlorzoxazone), Gin Pain Pills- Chlorzoxazone & Acetamin.Tab(Acetaminophen + Chlorzoxazone), Back-Aid Forte - Tab(Acetaminophen + Chlorzoxazone), Acetazone Forte C8(Acetaminophen + Chlorzoxazone + Codeine Phosphate), Parafon Forte C8 W Codeine Tab(Acetaminophen + Chlorzoxazone + Codeine Phosphate), Gin Pain Pills ... show more » Acetazone Forte(Acetaminophen + Chlorzoxazone), Gin Pain Pills- Chlorzoxazone & Acetamin.Tab(Acetaminophen + Chlorzoxazone), Back-Aid Forte - Tab(Acetaminophen + Chlorzoxazone), Acetazone Forte C8(Acetaminophen + Chlorzoxazone + Codeine Phosphate), Parafon Forte C8 W Codeine Tab(Acetaminophen + Chlorzoxazone + Codeine Phosphate), Gin Pain Pills - Tab(Acetaminophen + Chlorzoxazone), Extra Strength Tylenol Aches and Strains(Acetaminophen + Chlorzoxazone), Parafon Forte(Acetaminophen + Chlorzoxazone), Parafon Forte Tablets(Acetaminophen + Chlorzoxazone) show less «
Category:	Muscle Relaxants, Central
CAS number:	95-25-0

Pharmacology

Indication:	For the relief of discomfort associated with acute painful musculoskeletal conditions.
Pharmacology:	Chlorzoxazone, 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 musculosk... show more » Chlorzoxazone, 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. show less «
Mechanism of Action:	Chlorzoxazone 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 ... show more » Chlorzoxazone 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 show less «
Protein binding:	13-18%
Biotransformation:	Chlorzoxazone is rapidly metabolized in the liver and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Route of elimination:	Chlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Toxicity:	Oral, 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

Interactions

Food interaction:

Avoid alcohol.

Take without regard to meals.

Drug interaction:

Triprolidine	The CNS depressants, Triprolidine and Chlorzoxazone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Disulfiram	Disulfiram 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.

Targets

Calcium-activated potassium channel subunit alpha 1

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX)

UniProt ID:

Q12791

Gene:

KCNMA1

Actions:

inducer

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
View Article

Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
View Article

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.
View Article

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

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.
View Article

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
View Article

Enzymes

Transporters

Multidrug resistance protein 1