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Chemical Compound Review

Paraflex     5-chloro-3H-benzooxazol-2-one

Synonyms: Escoflex, Biomioran, Lorzone, Miotran, Parafon, ...
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Disease relevance of chlorzoxazone


Psychiatry related information on chlorzoxazone


High impact information on chlorzoxazone

  • Intravenous and oral midazolam (MDZ) clearances were used to measure the in vivo CYP3A activity, and chlorzoxazone (CHZ) oral clearance was used to assess in vivo CYP2E1 activity [6].
  • CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls [2].
  • Of the 52 substrates for the enzyme identified in this review, the demethylation of N,N-dimethylnitrosamine and the hydroxylation of p-nitrophenol and chlorzoxazone are the most effective for monitoring the level of this enzyme [7].
  • Chlorzoxazone was not a substrate for iNOS but was a potent competitive inhibitor with respect to L-Arg with Ki = 3.3+/-0.7 microM [8].
  • Characterization of inducible nitric-oxide synthase by cytochrome P-450 substrates and inhibitors. Inhibition by chlorzoxazone [8].

Chemical compound and disease context of chlorzoxazone


Biological context of chlorzoxazone


Anatomical context of chlorzoxazone

  • DTIC N-demethylation in a panel of 10 human liver microsome preparations was correlated with the catalytic activities for CYP1A2 (ethoxyresorufin O-deethylation and caffeine N3-demethylation) in the absence of alpha-naphthoflavone and with the catalytic activities for CYP2E1 (chlorzoxazone 6-hydroxylations) in the presence of alpha-naphthoflavone [18].
  • Genetic polymorphisms (Pst I and Rsa I restriction fragment length polymorphisms) in the 5'-flanking region of CYP2E1 deoxyribonucleic acid obtained from peripheral leukocytes were not associated with differences in the disposition of chlorzoxazone [16].
  • We demonstrated the presence of the CYP2E1 apoprotein in microsomes of RLECs by immunoblot analyses, together with chlorzoxazone 6-hydroxylation, an activity known to be mainly catalyzed by CYP2E1 [19].
  • These are open drugs of the skeletal muscle relaxant chlorzoxazone [20].
  • This study was carried out to test the specificity of such a substrate when first experiments conducted by using human hepatocyte cultures showed that the chlorzoxazone 6-hydroxylation activity increased after 3-methylcholanthrene treatment of cells [21].

Associations of chlorzoxazone with other chemical compounds


Gene context of chlorzoxazone


Analytical, diagnostic and therapeutic context of chlorzoxazone

  • At postoperative week 6 and year 1, the median body mass index (BMI) of subjects who underwent gastroplasty decreased by 11% and 33%, total oral CLZ clearance declined by 16% (P <.01) and 46% (P <.05), and Cl(u)/F decreased by 18% (P <.05) and 35% (P =.16), respectively [31].
  • Chlorzoxazone and the 6-hydroxy metabolite were measured by high-performance liquid chromatography [15].
  • METHODS: The plasma concentration-time profiles of chlorzoxazone and its 6-hydroxy metabolite were determined after oral administration of parent drug (250 mg) [3].
  • RESULTS: The chlorzoxazone metabolic ratio for the liver transplant patients in the first month after transplantation (mean +/- SD, 6.4 +/- 5.1) was significantly higher than that after 1 month after surgery (2.1 +/- 2.0), when the chlorzoxazone metabolic ratio was not different from control subjects (0.8 +/- 0.5) [32].
  • This results from hypothermia-induced decreases in the CYP2E1 enzyme affinity for the substrate chlorzoxazone [33].


  1. Chlorzoxazone-induced spasmotic torticollis. Rosin, M.A. JAMA (1981) [Pubmed]
  2. Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone. Rothman, N., Smith, M.T., Hayes, R.B., Traver, R.D., Hoener, B., Campleman, S., Li, G.L., Dosemeci, M., Linet, M., Zhang, L., Xi, L., Wacholder, S., Lu, W., Meyer, K.B., Titenko-Holland, N., Stewart, J.T., Yin, S., Ross, D. Cancer Res. (1997) [Pubmed]
  3. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. O'Shea, D., Davis, S.N., Kim, R.B., Wilkinson, G.R. Clin. Pharmacol. Ther. (1994) [Pubmed]
  4. Impaired 6-hydroxychlorzoxazone elimination in patients with kidney disease: Implication for cytochrome P450 2E1 pharmacogenetic studies. Nolin, T.D., Gastonguay, M.R., Bies, R.R., Matzke, G.R., Frye, R.F. Clin. Pharmacol. Ther. (2003) [Pubmed]
  5. Effects of glucose supplementation on the pharmacokinetics of intravenous chlorzoxazone in rats with water deprivation for 72 h. Kim, Y.C., Lee, I., Kim, S.G., Ko, S.H., Lee, M.G., Kim, S.H. Life Sci. (2006) [Pubmed]
  6. Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: a comparison with nonalcoholics. Liangpunsakul, S., Kolwankar, D., Pinto, A., Gorski, J.C., Hall, S.D., Chalasani, N. Hepatology (2005) [Pubmed]
  7. Oxidative and reductive metabolism by cytochrome P450 2E1. Koop, D.R. FASEB J. (1992) [Pubmed]
  8. Characterization of inducible nitric-oxide synthase by cytochrome P-450 substrates and inhibitors. Inhibition by chlorzoxazone. Grant, S.K., Green, B.G., Wang, R., Pacholok, S.G., Kozarich, J.W. J. Biol. Chem. (1997) [Pubmed]
  9. Kinetics of drug action in disease states. XXVII. Effect of experimental renal failure on the pharmacodynamics of zoxazolamine and chlorzoxazone. Yasuhara, M., Levy, G. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
  10. Effects of glucose on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate. Ahn, C.Y., Kim, E.J., Lee, I., Kwon, J.W., Kim, W.B., Kim, S.G., Lee, M.G. Journal of pharmaceutical sciences. (2003) [Pubmed]
  11. Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate. Chung, W., Kim, E.J., Lee, I., Kim, S.G., Lee, M.G., Kim, S.H. Life Sci. (2003) [Pubmed]
  12. Cytochrome P450 2E1: its clinical and toxicological role. Tanaka, E., Terada, M., Misawa, S. Journal of clinical pharmacy and therapeutics. (2000) [Pubmed]
  13. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Huang, Y.S., Chern, H.D., Su, W.J., Wu, J.C., Chang, S.C., Chiang, C.H., Chang, F.Y., Lee, S.D. Hepatology (2003) [Pubmed]
  14. The effect of endotoxin administration on the pharmacokinetics of chlorzoxazone in humans. Poloyac, S.M., Tosheva, R.T., Gardner, B.M., Shedlofsky, S.I., Blouin, R.A. Clin. Pharmacol. Ther. (1999) [Pubmed]
  15. Urinary excretion of 6-hydroxychlorzoxazone as an index of CYP2E1 activity. Dreisbach, A.W., Ferencz, N., Hopkins, N.E., Fuentes, M.G., Rege, A.B., George, W.J., Lertora, J.J. Clin. Pharmacol. Ther. (1995) [Pubmed]
  16. Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. Kim, R.B., O'Shea, D. Clin. Pharmacol. Ther. (1995) [Pubmed]
  17. Study of the fragmentation mechanism of protonated 6-hydroxychlorzoxazone: application in simultaneous analysis of CYP2E1 activity with major human cytochrome P450s. Anari, M.R., Bakhtiar, R., Franklin, R.B., Pearson, P.G., Baillie, T.A. Anal. Chem. (2003) [Pubmed]
  18. Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1. Reid, J.M., Kuffel, M.J., Miller, J.K., Rios, R., Ames, M.M. Clin. Cancer Res. (1999) [Pubmed]
  19. Rat liver epithelial cells express functional cytochrome P450 2E1. Lerche, C., Le Jossic, C., Fautrel, A., de Waziers, I., Ballet, F., Guillouzo, A., Corcos, L. Carcinogenesis (1996) [Pubmed]
  20. Cyclization-activated prodrugs: N-(substituted 2-hydroxyphenyl and 2-hydroxypropyl)carbamates based on ring-opened derivatives of active benzoxazolones and oxazolidinones as mutual prodrugs of acetaminophen. Vigroux, A., Bergon, M., Zedde, C. J. Med. Chem. (1995) [Pubmed]
  21. Both cytochromes P450 2E1 and 1A1 are involved in the metabolism of chlorzoxazone. Carriere, V., Goasduff, T., Ratanasavanh, D., Morel, F., Gautier, J.C., Guillouzo, A., Beaune, P., Berthou, F. Chem. Res. Toxicol. (1993) [Pubmed]
  22. Chlormethiazole inhibition of cytochrome P450 2E1 as assessed by chlorzoxazone hydroxylation in humans. Gebhardt, A.C., Lucas, D., Ménez, J.F., Seitz, H.K. Hepatology (1997) [Pubmed]
  23. Inhibition of chlorzoxazone metabolism, a clinical probe for CYP2E1, by a single ingestion of watercress. Leclercq, I., Desager, J.P., Horsmans, Y. Clin. Pharmacol. Ther. (1998) [Pubmed]
  24. Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1. Kharasch, E.D., Thummel, K.E., Mhyre, J., Lillibridge, J.H. Clin. Pharmacol. Ther. (1993) [Pubmed]
  25. Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine metabolism. Benowitz, N.L., Peng, M., Jacob, P. Clin. Pharmacol. Ther. (2003) [Pubmed]
  26. Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans. Lucas, D., Ferrara, R., Gonzalez, E., Bodenez, P., Albores, A., Manno, M., Berthou, F. Pharmacogenetics (1999) [Pubmed]
  27. Human cytochrome P450 2E1 (CYP2E1): from genotype to phenotype. Carrière, V., Berthou, F., Baird, S., Belloc, C., Beaune, P., de Waziers, I. Pharmacogenetics (1996) [Pubmed]
  28. Metabolism of vanoxerine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, by human cytochrome P450 enzymes. Cherstniakova, S.A., Bi, D., Fuller, D.R., Mojsiak, J.Z., Collins, J.M., Cantilena, L.R. Drug Metab. Dispos. (2001) [Pubmed]
  29. Identification of the main human cytochrome P450 enzymes involved in safrole 1'-hydroxylation. Ueng, Y.F., Hsieh, C.H., Don, M.J., Chi, C.W., Ho, L.K. Chem. Res. Toxicol. (2004) [Pubmed]
  30. An interaction between the cytochrome P450 probe substrates chlorzoxazone (CYP2E1) and midazolam (CYP3A). Palmer, J.L., Scott, R.J., Gibson, A., Dickins, M., Pleasance, S. British journal of clinical pharmacology. (2001) [Pubmed]
  31. CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Emery, M.G., Fisher, J.M., Chien, J.Y., Kharasch, E.D., Dellinger, E.P., Kowdley, K.V., Thummel, K.E. Hepatology (2003) [Pubmed]
  32. Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation. Burckart, G.J., Frye, R.F., Kelly, P., Branch, R.A., Jain, A., Fung, J.J., Starzl, T.E., Venkataramanan, R. Clin. Pharmacol. Ther. (1998) [Pubmed]
  33. Therapeutic hypothermia-induced pharmacokinetic alterations on CYP2E1 chlorzoxazone-mediated metabolism in a cardiac arrest rat model. Tortorici, M.A., Kochanek, P.M., Bies, R.R., Poloyac, S.M. Crit. Care Med. (2006) [Pubmed]
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