Chlorzoxazone acts primarily at the spinal cord and subcortical areas of the brain to inhibit multisynaptic reflex arcs involved in producing and maintaining muscle spasms. It inhibits mast cell degranulation, preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A). The compound may also act by inhibiting calcium and potassium influx, leading to neuronal inhibition and muscle relaxation. It is an activator of calcium-activated potassium channels.

In vitro, Chlorzoxazone has been shown to inhibit degranulation of mast cells. It acts as an activator of calcium-activated potassium channels. The compound demonstrates inhibitory activity on the multisynaptic reflex arcs in the spinal cord and brain subcortical areas. It also exhibits activity as a strong oxidizing agent.

In vivo, Chlorzoxazone acts as a centrally-acting agent for painful musculoskeletal conditions. Data from animal experiments and human studies indicate it acts primarily at the level of the spinal cord and subcortical areas of the brain. The clinical result is a reduction of skeletal muscle spasm with relief of pain and increased mobility. It is used for the relief of discomfort associated with acute painful musculoskeletal conditions.

In vitro enzyme/receptor binding assays for Chlorzoxazone typically involve studying its interaction with calcium-activated potassium channels. Membranes from cells expressing these channels are incubated with radiolabeled ligands in the presence of varying concentrations of Chlorzoxazone. Binding affinity and functional modulation can be assessed. Its oxidizing properties may also be evaluated in chemical assays.

Cell-based assays for Chlorzoxazone are performed using mast cell models to study its inhibitory effects on degranulation and the release of histamine and SRS-A. Cells are treated with the compound, and the release of these mediators is measured. Neuronal cell cultures may be used to assess its effects on calcium and potassium influx and its impact on neuronal activity.

Cellular assays for Chlorzoxazone are performed using mast cell models to study its inhibitory effects on degranulation and the release of histamine and SRS-A. Cells are treated with the compound, and the release of these mediators is measured. Neuronal cell cultures may be used to assess its effects on calcium and potassium influx and its impact on neuronal activity.

Absorption, Distribution and Excretion
Chlorzoxazone is rapidly metabolized and primarily excreted in the urine as a glucuronide conjugate. Metabolism/Metabolites Chlorzoxazone is rapidly metabolized in the liver and primarily excreted in the urine as a glucuronide conjugate. Known metabolites of chlorzoxazone include 6-hydroxychlorzoxazone.
Chlorzoxazone is well absorbed after oral administration. It is metabolized in the liver, primarily by cytochrome P450 enzymes, to 6-hydroxychlorzoxazone. The compound has a relatively short half-life. It is excreted in urine as metabolites. Its pharmacokinetic profile supports its use as an adjunctive therapy for acute musculoskeletal conditions.

Hepatotoxicity
Currently, there are insufficient prospective studies to confirm the incidence of elevated ALT or AST levels during chlorzoxazone treatment. A few clinically significant cases of liver disease may have been associated with chlorzoxazone, including some fatal ones. Due to the widespread use of this drug, such cases are inevitably very rare. Although case reports are few, chlorzoxazone has been clearly identified as a causative factor in many cases; furthermore, a structurally similar muscle relaxant (zoxazosamide) was discontinued in 1961 primarily due to its hepatotoxicity. The incubation period is typically 1 to 4 weeks, and the disease pattern is usually hepatocellular, characterized by significantly elevated ALT levels and jaundice, while alkaline phosphatase levels are less elevated. Elevated cholestatic enzymes have also been reported after exposure to chlorzoxazone. Allergic reactions (rash and fever) are common, especially in cases with short incubation periods (Case 1); autoantibodies are rare. Patients usually recover rapidly after discontinuing chlorzoxazone, but there are reports of disease progression leading to death even with early discontinuation (Case 2). Re-exposure to chlorzoxazone results in rapid recurrence of the injury, often accompanied by fever. Probability Score: B (Highly probable cause of clinically evident liver damage). Protein binding rate: 13-18%
Chlorzoxazone is generally well tolerated. Common side effects include drowsiness, dizziness, and gastrointestinal disturbances. It has a mild sedative property. Serious adverse effects are rare but may include hepatotoxicity. It should be used with caution in patients with liver impairment. The compound is contraindicated in patients with known hypersensitivity.

[1]. Comprehensive kinetic analysis and influence of reaction components for chlorzoxazone 6-hydroxylation in human liver microsomes with CYP antibodies. Xenobiotica. 2015 Apr;45(4):353-360.

Chlorzoxazone belongs to the 1,3-benzoxazole class of compounds, with the structure 1,3-benzoxazole-2-ol, where the hydrogen atom at position 5 is replaced by a chlorine atom. It is a centrally acting muscle relaxant with sedative effects, used to relieve pain caused by muscle spasms. It is both a muscle relaxant and a sedative. Chlorzoxazone belongs to the 1,3-benzoxazole class of compounds, organochlorine compounds, and heteroaryl hydroxyl compounds. It is a centrally acting muscle relaxant with sedative effects. It is claimed to inhibit muscle spasms primarily by acting on the spinal cord and subcortical regions of the brain. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 1202) Chlorzoxazone is a muscle relaxant. The physiological effects of chlorzoxazone are achieved through centrally mediated muscle relaxation. Chlorzoxazone is a centrally acting muscle relaxant commonly used to treat low back pain. Chlorzoxazone has been associated with rare cases of acute liver injury, some of which have even led to death. Chlorzoxazone is a benzoxazolone derivative with mild sedative and central muscle relaxant effects. Although its exact mechanism of action is unclear, chlorzoxazone (CZ) appears to act on the spinal cord and subcortical regions of the brain, inhibiting polysynaptic reflex arcs involved in the generation and maintenance of muscle spasms. The drug is extensively hydroxylated to 6-hydroxychlorzoxazone (HCZ)^11,12 via cytochrome P450 2E1 (CYP2E1), followed by glucuronidation and renal excretion. CZ is highly selective for CYP2E1 and can be used as a selective probe for human CYP2E1 phenotypic analysis; the plasma HCZ/CZ concentration ratio obtained 2 to 4 hours after oral administration of CZ can serve as a phenotypic indicator of CYP2E1 enzyme activity. A central muscle relaxant with sedative effects. It is claimed to inhibit muscle spasms primarily through its action on the spinal cord and subcortical regions of the brain. (Excerpt from Martindale Pharmacopoeia, 30th Edition, p. 1202) Indications: For the relief of discomfort caused by acute painful musculoskeletal disorders. Mechanism of Action: Chlorzoxazone inhibits mast cell degranulation, thereby preventing the release of histamine and slow-reacting anaphylactic substances (SRS-A, mediators of type I hypersensitivity reactions). Chlorzoxazone also reduces the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium-potassium influx, leading to neuronal inhibition and muscle relaxation. Data from animal and human studies indicate that chlorzoxazone primarily acts on the spinal cord and subcortical regions of the brain, inhibiting polysynaptic reflex arcs involved in the generation and maintenance of skeletal muscle spasticity. Pharmacodynamics: Chlorzoxazone is a centrally acting drug used to treat painful musculoskeletal disorders. Data from animal experiments and human studies indicate that chlorzoxazone primarily acts on the spinal cord and subcortical regions of the brain, inhibiting polysynaptic reflex arcs involved in the generation and maintenance of skeletal muscle spasms caused by various etiologies. Clinical efficacy includes reducing skeletal muscle spasms, relieving pain, and increasing the range of motion of affected muscles.
Chlorzoxazone is a centrally acting muscle relaxant approved for the relief of discomfort associated with acute painful musculoskeletal conditions. It is available as an oral tablet, often in combination with other analgesics like acetaminophen. The compound is on the WHO Model List of Essential Medicines. Its mechanism of action is distinct from other muscle relaxants, making it a valuable therapeutic option.

C7H4CLNO2

169.56

168.993

95-25-0

Chlorzoxazone-d3;1185173-60-7;Chlorzoxazone-13C;616865-28-2

2733

White to off-white solid powder

1.5±0.1 g/cm3

336.9±34.0 °C at 760 mmHg

191-192 °C(lit.)

157.5±25.7 °C

0.0±0.8 mmHg at 25°C

1.674

2.29

1

2

0

11

185

0

TZFWDZFKRBELIQ-UHFFFAOYSA-N

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

5-chloro-3H-1,3-benzoxazol-2-one

5-Chloro-2-benzoxazolone; Paraflex; Chlorzoxazone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~589.73 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (14.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (14.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)