Its name derives from its systematic name, dimethylphenylaminobenzoic acid. It was discovered and brought to market byParke-Davis as Ponstel in the 1960s. It became generic in the 1980s and is available worldwide under many brand names such asMeftal.[5]
There is evidence that supports the use of mefenamic acid for perimenstrualmigraine headache prophylaxis, with treatment starting two days prior to the onset of flow or one day prior to the expected onset of the headache and continuing for the duration ofmenstruation.[4]
Mefenamic acid is recommended to be taken with food.[11]
In October 2020, the USFood and Drug Administration (FDA) required the prescribing information to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[16][17] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[16][17]
Like other members of the anthranilic acid derivatives (or fenamate) class ofNSAIDs, it inhibits both isoforms of the enzymecyclooxygenase (COX-1 andCOX-2). This prevents formation ofprostaglandins,[14][19] which play a role in pain sensitivity, inflammation and fever, but also inhemostasis, kidney function, sustaining of pregnancy, and protection of thegastric mucosa.[20]
Mefenamic acid (top) and its 3'-hydroxymethyl- and 3'-carboxy-metabolites (middle and bottom, respectively). Thecarboxy groups at the bottom right of each substance can beglucuronidized.
Mefenamic acid is rapidly absorbed from the gut and reaches highest concentrations in theblood plasma after one to four hours. When in the bloodstream, over 90% of the substance are bound toplasma proteins. It probably crosses theplacenta, and is found in the breast milk in small amounts.[7][12]
It is metabolized by the liver enzymeCYP2C9 to the only weakly active 3'-hydroxymethylmefenamic acid. 3'-carboxymefenamic acid has also been identified as a metabolite, as well ascarboxyglucuronides of all three substances. Mefenamic acid and its metabolites are excreted via the urine (52–67%) and the faeces (20–25%, or less than 20% following another source). The parent substance has abiological half-life of two hours; the half-life of its metabolites may be longer.[7][8][12]
Mefenamic acid, a member of the fenamate, is a chemical compound derived from anthranilic acid . This derivative is created by substituting one of the hydrogen atoms attached to the nitrogen atom with a 2,3-dimethylphenyl fragment. The result is a structurally complex molecule with fascinating conformational properties.
The mefenamic acid molecule exhibits conformational lability, meaning it can exist in various shapes or conformers. This flexibility arises from changes in the position of the carboxylic acid group and the 2,3-dimethylphenyl fragment about the anthranil moiety. Specifically, the arrangement of the substituted benzene fragments relative to each other plays a crucial role in determining the different polymorphic forms of mefenamic acid.[25]
Recent experimental studies have unveiled two additional hidden conformers of mefenamic acid.[26] These conformers result from alterations in the positions of hydroxyl groups within the molecule. This discovery adds to our understanding of the compound's structural diversity.
External factors, including temperature, pressure, and the surrounding medium, highly influence the conformational state of mefenamic acid. Researchers have conducted extensive investigations into its spatial structure not only in organic solvents[27] but also in supercritical fluids,[28][29] aerogels,[30] and lipid bilayers.[31][32] These studies have helped elucidate the impact of different environments on the molecule's conformation.
Mefenamic acid is generic and is available worldwide under many brand names.[5]
In the US, wholesale price of a week's supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70.[33] By contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.[34] In New Zealand, a weeks's supply of Ponstan costs NZ$9.08, around US$5.50.[35]
While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models ofAlzheimer's disease[36][37] there is little evidence that mefenamic acid or other NSAIDs can treat or prevent Alzheimer's in humans; clinical trials of NSAIDs other than mefenamic acid for treatment of Alzheimer's have found more harm than benefit.[38][39][40] A small controlled study of 28 human subjects showed improved cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy.[41]
^Aronson JK (2010).eyler's Side Effects of Analgesics and Anti-inflammatory Drugs. Amsterdam: Elsevier Science. p. 334.ISBN978-0-08-093294-1.
^abc"Mefenamic Acid".LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. January 2020.PMID31643361. Retrieved28 November 2019.
^Khodov IA, Belov KV, Efimov SV, de Carvalho LA (January 2019).Determination of preferred conformations of mefenamic acid in DMSO by NMR spectroscopy and GIAO calculation. AIP Conference Proceedings. Vol. 2063. AIP Publishing. p. 040007.doi:10.1063/1.5087339.
^Khodov I, Sobornova V, Mulloyarova V, Belov K, Dyshin A, de Carvalho LB, et al. (August 2023). "Does DMSO affect the conformational changes of drug molecules in supercritical CO2 Media?".Journal of Molecular Liquids.384 122230.doi:10.1016/j.molliq.2023.122230.S2CID259822531.
^Khodov IA, Musabirova GS, Klochkov VV, Karataeva FK, Huster D, Scheidt HA (December 2022). "Structural details on the interaction of fenamates with lipid membranes".Journal of Molecular Liquids.367 120502.doi:10.1016/j.molliq.2022.120502.S2CID252747244.
^Joo Y, Kim HS, Woo RS, Park CH, Shin KY, Lee JP, et al. (January 2006). "Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models".Molecular Pharmacology.69 (1):76–84.doi:10.1124/mol.105.015206.PMID16223958.S2CID20982844.
^Miguel-Álvarez M, Santos-Lozano A, Sanchis-Gomar F, Fiuza-Luces C, Pareja-Galeano H, Garatachea N, et al. (February 2015). "Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect".Drugs & Aging.32 (2):139–147.doi:10.1007/s40266-015-0239-z.PMID25644018.S2CID35357112.
^Wang J, Tan L, Wang HF, Tan CC, Meng XF, Wang C, et al. (2015). "Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis".Journal of Alzheimer's Disease.44 (2):385–396.doi:10.3233/JAD-141506.PMID25227314.
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