Metaxalone

Metaxalone
Clinical data
Trade namesSkelaxin
AHFS/Drugs.comMonograph
MedlinePlusa682010
License data
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
BioavailabilityUnknown
MetabolismLiver
Elimination half-life9.2 ± 4.8 hours
ExcretionKidney
Identifiers
  • 5-[(3,5-dimethylphenoxy)methyl]-1,3-oxazolidin-2-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.015.253 Edit this at Wikidata
Chemical and physical data
FormulaC12H15NO3
Molar mass221.256 g·mol−1
3D model (JSmol)
  • O=C2OC(COc1cc(cc(c1)C)C)CN2
  • InChI=1S/C12H15NO3/c1-8-3-9(2)5-10(4-8)15-7-11-6-13-12(14)16-11/h3-5,11H,6-7H2,1-2H3,(H,13,14)
  • Key:IMWZZHHPURKASS-UHFFFAOYSA-N

Metaxalone, sold under the brand name Skelaxin, is a muscle relaxant medication used to relax muscles and relieve pain caused by strains, sprains, and other musculoskeletal conditions. It is a moderately strong muscle relaxant, with relatively low incidence of side effects. Its exact mechanism of action is not known, but it may be due to general central nervous system depression. Studies in vitro have shown metaxalone to suppress production of pro-inflammatory cytokines such as TNF-α and IL-6 and increase production of the antiinflammatory cytokine IL-13, however it also inhibits MAO-A and this may both contribute to its therapeutic effects and also is linked to toxicity in overdose.

Common side effects include nausea, vomiting, drowsiness, and central nervous system (CNS) side effects, such as dizziness, headache, and irritability.

The metabolism of metaxalone involves enzymes CYP1A2 and CYP2C19 in the cytochrome P450 system. [medical citation needed] Because many medications are metabolized by enzymes in this system, precaution must be taken when administering it with other medications involving the P450 system to avoid interactions.

Because of the potential for side effects, this drug is considered high risk in the elderly.[medical citation needed]

Pharmacokinetics

Metaxalone exhibits increased bioavailability when taken with food. Specifically, in one study, compared to fasted conditions, the presence of food at the time of drug administration increased Cmax by 77.5%, AUC0-t by 23.5%, and AUC0-∞ by 15.4%. Metaxalone is a substrate of CYP1A2 and CYP2C19, an inhibitor of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A, and an inducer of CYP1A2 and CYP3A4.

Assay

Nirogi et al. reported a liquid chromatographic method coupled to tandem mass spectrometry for the quantification of metaxalone in human plasma. A stability-indicating HPLC method was introduced by P. K. Sahu et al. Metaxalone has been used as an internal standard for few analytical methods.

References

  1. 1 2 3 4 "Skelaxin- metaxalone tablet". DailyMed. U.S. National Library of Medicine. 27 April 2018. Retrieved 23 October 2020.
  2. ↑ Elenbaas JK (October 1980). "Centrally acting oral skeletal muscle relaxants". American Journal of Hospital Pharmacy. 37 (10): 1313–1323. PMID 6999895.
  3. ↑ Harden RN, Argoff C (January 2000). "A review of three commonly prescribed skeletal muscle relaxants". Journal of Back and Musculoskeletal Rehabilitation. 15 (2): 63–66. doi:10.3233/bmr-2000-152-303. PMID 22388444.
  4. ↑ Toth PP, Urtis J (September 2004). "Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone". Clinical Therapeutics. 26 (9): 1355–1367. doi:10.1016/j.clinthera.2004.09.008. PMID 15530999.
  5. ↑ Yamaguchi M, Levy RM (2020). "Metaxalone Suppresses Production of Inflammatory Cytokines Associated with Painful Conditions in Mouse Macrophages RAW264.7 Cells in Vitro: Synergistic Effect with β-caryophyllene". Current Molecular Medicine. 20 (8): 643–652. doi:10.2174/1566524020666200217102508. PMID 32065089.
  6. ↑ Pallio G, d'Ascola A, Cardia L, Mannino F, Bitto A, Minutoli L, et al. (August 2021). "MAO-A Inhibition by Metaxalone Reverts IL-1β-Induced Inflammatory Phenotype in Microglial Cells". International Journal of Molecular Sciences. 22 (16): 8425. doi:10.3390/ijms22168425. PMC 8395141. PMID 34445126.
  7. ↑ Martini DI, Nacca N, Haswell D, Cobb T, Hodgman M (March 2015). "Serotonin syndrome following metaxalone overdose and therapeutic use of a selective serotonin reuptake inhibitor". Clinical Toxicology. 53 (3). Philadelphia, Pa.: 185–187. doi:10.3109/15563650.2015.1009993. PMID 25671244.
  8. ↑ Cherrington B, Englich U, Niruntari S, Grant W, Hodgman M (May 2020). "Monoamine oxidase A inhibition by toxic concentrations of metaxalone". Clinical Toxicology. 58 (5). Philadelphia, Pa.: 383–387. doi:10.1080/15563650.2019.1648815. PMID 31373522.
  9. 1 2 US patent 7378434, Du J, Roberts RH, "Metaxalone products, method of manufacture, and method of use", published 27 May 2008, issued 27 May 2008, assigned to Takeda Pharmaceuticals USA Inc. and Mutual Pharmaceutical Company, Inc.
  10. ↑ "Skelaxin Package Insert". King Pharmaceuticals, Inc. Archived from the original on 9 March 2010.
  11. 1 2 Nirogi RV, Kandikere VN, Shukla M, Mudigonda K, Shrivastava W, Datla PV (May 2006). "Quantification of metaxalone in human plasma by liquid chromatography coupled to tandem mass spectrometry". Journal of Analytical Toxicology. 30 (4): 245–251. doi:10.1093/jat/30.4.245. PMID 16803662.
  12. ↑ Sahu PK, Annapurna MM, Kumar SD (2011). "Development and Validation of Stability Indicating RP-HPLC Method for the Determination of Metaxalone in Bulk and its Pharmaceutical Formulations". Journal of Chemistry. 8 (s1): S439–S447. doi:10.1155/2011/645710.
  13. ↑ Mistri HN, Jangid AG, Pudage A, Gomes N, Sanyal M, Shrivastav P (June 2007). "High throughput LC-MS/MS method for simultaneous quantification of lamivudine, stavudine and nevirapine in human plasma". Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 853 (1–2): 320–332. doi:10.1016/j.jchromb.2007.03.047. PMID 17481969.
  14. ↑ Mistri HN, Jangid AG, Pudage A, Shrivastav P (March 2008). "HPLC-ESI-MS/MS validated method for simultaneous quantification of zopiclone and its metabolites, N-desmethyl zopiclone and zopiclone-N-oxide in human plasma". Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 864 (1–2): 137–148. doi:10.1016/j.jchromb.2008.02.004. PMID 18313371.