View source for Mefenamic acid

{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 476997443
| IUPAC_name = 2-(2,3-dimethylphenyl)aminobenzoic acid
| image = Mefenamic_acid2DACS.svg
| image_class = skin-invert-image
| width = 150
| alt = 
| image2 = Mefenamic-acid-from-xtal-3D-bs-17.png
| image_class2 = bg-transparent
| width2 =
| alt2 = 

<!--Clinical data-->
| tradename = Ponstel, Ponstan, others
| Drugs.com = {{drugs.com|monograph|mefenamic_acid}}
| MedlinePlus = a681028
| pregnancy_AU = C
| routes_of_administration = [[Oral administration|By mouth]], [[Rectal administration|rectal]]
| ATC_prefix = M01
| ATC_suffix = AG01

| legal_AU = S2
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=[[Health Canada]] | date=6 June 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=8 June 2024}}</ref>
| legal_US = Rx-only
| legal_UK = POM

<!--Pharmacokinetic data-->
| bioavailability = 90%
| protein_bound = >90%
| metabolism = [[Liver]] ([[CYP2C9]])
| elimination_half-life = 2 hours
| excretion = [[Kidney]] (52–67%), faeces (20–25%)

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 61-68-7
| PubChem = 4044
| IUPHAR_ligand = 2593
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00784
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3904
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 367589PJ2C
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00151
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6717
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 686

<!-- Chemical data -->
| C=15 | H=15 | N=1 | O=2
| SMILES = O=C(O)c2c(Nc1cccc(c1C)C)cccc2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H15NO2/c1-10-6-5-9-13(11(10)2)16-14-8-4-3-7-12(14)15(17)18/h3-9,16H,1-2H3,(H,17,18)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HYYBABOKPJLUIN-UHFFFAOYSA-N
}}

'''Mefenamic acid''' is a member of the [[Nonsteroidal anti-inflammatory drug#Anthranilic acid derivatives .28fenamates.29|anthranilic acid derivatives]] (or fenamate) class of [[nonsteroidal anti-inflammatory drug]]s (NSAIDs), and is used to treat mild to moderate pain.<ref name="Label">{{cite web | publisher = U.S. Food and Drug Administration | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/015034s040lbl.pdf | title = Ponstel Label | date = 19 February 2008 }}</ref><ref name=Pringsheim/>

Its name derives from its systematic name, di'''me'''thyl'''phen'''yl'''am'''inobenzo'''ic acid'''. It was discovered and brought to market by [[Parke-Davis]] as Ponstel in the 1960s. It became generic in the 1980s and is available worldwide under many brand names such as ''Meftal''.<ref name=BrandNames/>

==Medical uses==
Mefenamic acid is used to treat pain and inflammation in [[rheumatoid arthritis]] and [[osteoarthritis]], postoperative pain, acute pain including [[muscle pain|muscle]] and [[back pain]], [[toothache]] and [[dysmenorrhoea|menstrual pain]], as well as being prescribed for [[menorrhagia]].<ref>{{Cite journal|url=https://about.medicinescomplete.com/|title=Digital Medicines Information Suite|website=MedicinesComplete|language=en-GB|doi=10.18578/bnf.855907230|access-date=2020-04-18|url-access=subscription}}</ref><ref name="AustriaCodex" /><ref name="mediQ" /> In a 10-year study, mefenamic acid and other oral medicines ([[tranexamic acid]]) were as effective as the [[Hormonal intrauterine device|levonorgestrel intrauterine coil]]; the same proportion of women had not had surgery for heavy bleeding and had similar improvements in their quality of life.<ref>{{cite journal | vauthors = Kai J, Dutton B, Vinogradova Y, Hilken N, Gupta J, Daniels J | title = Rates of medical or surgical treatment for women with heavy menstrual bleeding: the ECLIPSE trial 10-year observational follow-up study | language = EN | journal = Health Technology Assessment | volume = 27 | issue = 17 | pages = 1–50 | date = October 2023 | pmid = 37924269 | pmc = 10641716 | doi = 10.3310/JHSW0174 }}</ref><ref>{{Cite journal |date=8 March 2024 |title=The coil and medicines are both effective long-term treatments for heavy periods |url=https://evidence.nihr.ac.uk/alert/the-coil-and-medicines-are-both-effective-long-term-treatments-for-heavy-periods/ |journal=NIHR Evidence|doi=10.3310/nihrevidence_62335 |url-access=subscription }}</ref>

There is evidence that supports the use of mefenamic acid for perimenstrual [[migraine 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 of [[menstruation]].<ref name=Pringsheim>{{cite journal | vauthors = Pringsheim T, Davenport WJ, Dodick D | title = Acute treatment and prevention of menstrually related migraine headache: evidence-based review | journal = Neurology | volume = 70 | issue = 17 | pages = 1555–1563 | date = April 2008 | pmid = 18427072 | doi = 10.1212/01.wnl.0000310638.54698.36 | s2cid = 27966664 }}</ref>

Mefenamic acid is recommended to be taken with food.<ref>{{ cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/meds/a681028.html#side-effects | publisher = National Institutes of Health | work = Medline Plus | title = Side effects for Mefenamic Acid }}</ref>

==Contraindications==
Mefenamic acid is contraindicated in people who have shown [[hypersensitivity]] reactions such as [[urticaria]] and [[asthma]] to this drug or to other NSAIDs (e.g. [[aspirin]]); those with [[peptic ulcer]]s or chronic inflammation of the [[gastrointestinal tract]]; those with [[kidney disease|kidney]] or [[liver disease]]; [[heart failure]]; after [[coronary artery bypass surgery]]; and during the third trimester of pregnancy.<ref name="AustriaCodex" /><ref name="Drugs.com" />

==Side effects==
Known mild [[Adverse drug reaction|side effects]] of mefenamic acid include [[headache]]s, nervousness, and [[vomiting]]. Potentially serious side effects may include [[diarrhea]], [[gastrointestinal perforation]], peptic ulcers, [[hematemesis]] (vomiting blood), skin reactions (rashes, itching, swelling; in rare cases [[toxic epidermal necrolysis]]) and rarely blood cell disorders such as [[agranulocytosis]].<ref name=Aronson>{{cite book | vauthors = Aronson JK |title=eyler's Side Effects of Analgesics and Anti-inflammatory Drugs |date=2010 |publisher=Elsevier Science |location=Amsterdam |isbn=978-0-08-093294-1 | page = 334 }}</ref><ref name="AustriaCodex" /> It has been associated with acute liver damage.<ref name=LiverTox/>

In 2008 the US label was updated with a warning concerning a risk of premature closure of the [[ductus arteriosus]] in pregnancy.<ref>{{cite web | publisher = U.S. Food and Drug Administration | date = March 2008 | url = https://www.fda.gov/safety/medwatch/safetyinformation/safety-relateddruglabelingchanges/ucm116459.htm | archive-url = https://web.archive.org/web/20091104195526/https://www.fda.gov/safety/medwatch/safetyinformation/safety-relateddruglabelingchanges/ucm116459.htm | archive-date = 4 November 2009 | title = Safety Labeling Changes: Ponstel (mefenamic acid capsules, USP) | work = Center for Drug Evaluation and Research (CDER) }}</ref>

In October 2020, the U.S. [[Food and Drug Administration]] (FDA) required the [[Drug labelling|drug label]] 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.<ref name="FDA PR 20201015" /><ref name="FDA safety 20201015" /> They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.<ref name="FDA PR 20201015">{{cite press release | title=FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 October 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-warns-using-type-pain-and-fever-medication-second-half-pregnancy-could-lead-complications | access-date=15 October 2020}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} {{PD-notice}}</ref><ref name="FDA safety 20201015">{{cite web | title=NSAIDs may cause rare kidney problems in unborn babies | website=U.S. Food and Drug Administration | date=21 July 2017 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic | access-date=15 October 2020}} {{PD-notice}}</ref>

In its November 2023 monthly drug safety alert under the [[Pharmacovigilance Programme of India]] (PvPI), the [[Indian Pharmacopoeia Commission]] flagged a risk of [[Drug rash with eosinophilia and systemic symptoms|DRESS Syndrome]] due to use of mefenamic acid.<ref>{{Cite web |date=30 November 2023 |title=Monthly Drug Safety Alert |url=https://ipc.gov.in/8-category-en/1089-drug-alerts-2023.html |access-date=10 December 2023 |website=Indian Pharmacopoeia Commission}}</ref>

==Overdose==
Symptoms of overdosing include [[kidney failure]], [[gastrointestinal]] problems, bleeding, rashes, confusion, [[hallucination]]s, [[vertigo]], [[seizure]]s, and loss of consciousness. It is treated with induction of vomiting, [[gastric lavage]], [[bone char]], and control of [[electrolytes]] and vital functions.<ref name="AustriaCodex" />

== Interactions ==

Interactions are broadly similar to those of other NSAIDs. Mefenamic acid interferes with the anti–blood clotting mechanism of Aspirin. It increases the [[Anticoagulant|blood thinning]] effects of [[warfarin]] and [[phenprocoumon]] because it displaces them from their [[plasma protein]] binding and increases their free concentrations in the bloodstream. It adds to the risk of gastrointestinal ulcera associated with [[corticosteroid]]s and [[selective serotonin reuptake inhibitor]]s. It can increase the risk for adverse effects of [[methotrexate]] and [[lithium (medication)|lithium]] by lowering their excretion via the kidneys. It can increase the kidney toxicity of [[ciclosporin]] and [[tacrolimus]]. Combination with [[antihypertensive drug]]s such as [[ACE inhibitor]]s, [[sartan]]s and [[diuretic]]s can decrease their effectiveness as well as increase the risk for kidney toxicity.<ref name="AustriaCodex" /><ref name="mediQ">{{cite web|url=https://www.mediq.ch/|title=mediQ: Mefenaminsäure|access-date=2020-07-23}}</ref>

==Pharmacology==
===Mechanism of action===
{{main|Nonsteroidal anti-inflammatory drug#Mechanism of action}}
Like other members of the anthranilic acid derivatives (or fenamate) class of [[NSAID]]s, it inhibits both isoforms of the enzyme [[cyclooxygenase]] ([[COX-1]] and [[COX-2]]). This prevents formation of [[prostaglandin]]s,<ref name=LiverTox>{{cite book | chapter = Mefenamic Acid | title =LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet] | location = Bethesda (MD) | publisher = National Institute of Diabetes and Digestive and Kidney Diseases | date = January 2020 | chapter-url = https://www.ncbi.nlm.nih.gov/books/n/livertox/MefenamicAcid/ | access-date = 28 November 2019 | pmid = 31643361 }}</ref><ref>{{cite journal | vauthors = Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ | title = Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid | journal = Biochemistry | volume = 48 | issue = 31 | pages = 7353–7355 | date = August 2009 | pmid = 19603831 | pmc = 2720641 | doi = 10.1021/bi900999z }}</ref> which play a role in pain sensitivity, inflammation and fever, but also in [[hemostasis]], kidney function, sustaining of pregnancy, and protection of the [[gastric mucosa]].<ref>{{cite book|title=Arzneimittelwirkungen| vauthors = Mutschler E |year=2013 |publisher=Wissenschaftliche Verlagsgesellschaft Stuttgart|isbn=978-3-8047-2898-1|pages=205–206, 444}}</ref>

===Pharmacokinetics===
[[File:Mefenamic acid metabolites.svg|class=skin-invert-image|thumb|upright=0.75|Mefenamic acid (top) and its 3'-hydroxymethyl- and 3'-carboxy-metabolites (middle and bottom, respectively). The [[carboxy]] groups at the bottom right of each substance can be [[Glucuronidation|glucuronidized]].]]
Mefenamic acid is rapidly absorbed from the gut and reaches highest concentrations in the [[blood plasma]] after one to four hours. When in the bloodstream, over 90% of the substance are bound to [[plasma protein]]s. It probably crosses the [[placenta]], and is found in the breast milk in small amounts.<ref name="AustriaCodex">{{cite book|title=Austria-Codex|publisher=Österreichischer Apothekerverlag|location=Vienna|at=Parkemed 500&nbsp;mg-Filmtabletten|year=2020|language=de}}</ref><ref name="Drugs.com">{{cite web | author = Cerner Multum | title = Mefenamic Acid | url = https://www.drugs.com/mtm/mefenamic-acid.html | access-date = 2020-07-22 | work = Drugs.com }}</ref>

It is metabolized by the liver enzyme [[CYP2C9]] to the only weakly active 3'-hydroxymethylmefenamic acid. 3'-carboxymefenamic acid has also been identified as a metabolite, as well as [[carboxy]] [[glucuronide]]s 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 a [[biological half-life]] of two hours; the half-life of its metabolites may be longer.<ref name="AustriaCodex" /><ref name="mediQ" /><ref name="Drugs.com" />

==History==
Scientists led by Claude Winder from [[Parke-Davis]] invented mefenamic acid in 1961, along with fellow members of the class of [[Nonsteroidal anti-inflammatory drug#Anthranilic acid derivatives .28fenamates.29|anthranilic acid derivatives]], [[flufenamic acid]] in 1963 and [[meclofenamate sodium]] in 1964.<ref name="Whitehouse_2009">{{cite journal | vauthors = Whitehouse MW | title = Drugs to treat inflammation: a historical introduction | journal = Current Medicinal Chemistry | volume = 4| pages = 707–729 (718) | date = 2009 | issue = 25 | pmid = 16378496 | doi = 10.2174/092986705774462879 | isbn = 978-1-60805-207-3 }}</ref>  U.S. Patent 3,138,636 on the drug was issued in 1964.<ref>{{cite patent | country = US | number = 3,138,636 | inventor = Scherrer RA | assign1 = Parke Davis and Co LLC | gdate = 23 June 1964 | url = https://www.google.com/patents/US3138636 }}</ref><ref name=Sittig/>

It was approved in the UK in 1963 as ''Ponstan'', in West Germany in 1964 as ''Ponalar'' and in France as ''Ponstyl'', and the US in 1967 as ''Ponstel''.<ref name=LiverTox/><ref name=Sittig>{{cite book | vauthors = Sittig M | chapter = Mefenamic acid | pages = 918–919 | url = http://files.rushim.ru/books/lekarstva/pharmaceutical-encyclopedia.pdf | title = Pharmaceutical Manufacturing Encyclopedia | volume = 1 | archive-url = https://web.archive.org/web/20071023210611/http://files.rushim.ru/books/lekarstva/pharmaceutical-encyclopedia.pdf | archive-date=2007-10-23 | edition = Second | publisher = Noyes Publications | date = 1988 }}</ref>

==Chemistry==
===Synthesis===
Analogous to [[fenamic acid]], this compound may be made from [[2-chlorobenzoic acid]] and [[2,3-dimethylaniline]].<ref>{{ cite journal | vauthors = Trinus FP, Mokhort NA, Yagupol'skii LM, Fadeicheva AG, Danilenko VS, Ryabukha TK, Fialkov YA, Kirichek LM, Endel'man ÉS, Get'man GA | s2cid = 45211486 | title = Mefenamic acid — A Nonsteroid Antiinflammatory Agent | journal = Pharmaceutical Chemistry Journal | year = 1977 | volume = 11 | issue = 12 | pages = 1706–1711 | doi = 10.1007/BF00778304 }}</ref>

=== Conformational flexibility ===
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.<ref>{{Cite journal | vauthors = SeethaLekshmi S, Guru Row TN |date= August 2012 |title=Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid |journal=Crystal Growth & Design |language=en |volume=12 |issue=8 |pages=4283–4289 |doi=10.1021/cg300812v |issn=1528-7483}}</ref>

Recent experimental studies have unveiled two additional hidden conformers of mefenamic acid.<ref>{{cite journal | vauthors = Belov KV, Batista de Carvalho LA, Dyshin AA, Efimov SV, Khodov IA | title = The Role of Hidden Conformers in Determination of Conformational Preferences of Mefenamic Acid by NOESY Spectroscopy | journal = Pharmaceutics | volume = 14 | issue = 11 | pages = 2276 | date = October 2022 | pmid = 36365095 | pmc = 9696638 | doi = 10.3390/pharmaceutics14112276 | doi-access = free }}</ref> 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<ref>{{Cite conference | vauthors = Khodov IA, Belov KV, Efimov SV, de Carvalho LA |title=Determination of preferred conformations of mefenamic acid in DMSO by NMR spectroscopy and GIAO calculation | conference = AIP Conference Proceedings | date = January 2019 | volume = 2063 | issue = 1 | publisher = AIP Publishing. |pages=040007 |doi=10.1063/1.5087339}}</ref> but also in supercritical fluids,<ref>{{Cite journal | vauthors = Belov KV, Batista de Carvalho LA, Dyshin AA, Kiselev MG, Sobornova VV, Khodov IA |date=December 2022 |title=Conformational Analysis of Mefenamic Acid in scCO2-DMSO by the 2D NOESY Method |journal=Russian Journal of Physical Chemistry B |language=en |volume=16 |issue=7 |pages=1191–1199 |doi=10.1134/S1990793122070028 |bibcode=2022RJPCB..16.1191B |s2cid=256259116 |issn=1990-7931}}</ref><ref>{{Cite journal | vauthors = Khodov I, Sobornova V, Mulloyarova V, Belov K, Dyshin A, de Carvalho LB, Tolstoy P, Kiselev M |date=August 2023 |title=Does DMSO affect the conformational changes of drug molecules in supercritical CO2 Media? |journal=Journal of Molecular Liquids |language=en |volume=384 |pages=122230 |doi=10.1016/j.molliq.2023.122230|s2cid=259822531 }}</ref> aerogels,<ref>{{cite journal | vauthors = Khodov I, Sobornova V, Mulloyarova V, Belov K, Dyshin A, de Carvalho LB, Tolstoy P, Kiselev M | title = Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis | journal = International Journal of Molecular Sciences | volume = 24 | issue = 8 | pages = 6882 | date = April 2023 | pmid = 37108046 | pmc = 10138679 | doi = 10.3390/ijms24086882 | doi-access = free }}</ref> and lipid bilayers.<ref>{{Cite journal | vauthors = Khodov IA, Musabirova GS, Klochkov VV, Karataeva FK, Huster D, Scheidt HA |date=December 2022 |title=Structural details on the interaction of fenamates with lipid membranes |journal=Journal of Molecular Liquids |language=en |volume=367 |pages=120502 |doi=10.1016/j.molliq.2022.120502|s2cid=252747244 }}</ref><ref>{{cite journal | vauthors = Khodov IA, Belov KV, Huster D, Scheidt HA | title = Conformational State of Fenamates at the Membrane Interface: A MAS NOESY Study | journal = Membranes | volume = 13 | issue = 6 | pages = 607 | date = June 2023 | pmid = 37367811 | pmc = 10300900 | doi = 10.3390/membranes13060607 | doi-access = free }}</ref> These studies have helped elucidate the impact of different environments on the molecule's conformation.

==Society and culture==
===Availability and pricing===
Mefenamic acid is generic and is available worldwide under many brand names.<ref name=BrandNames>{{cite web | work = Drugs.com | url = https://www.drugs.com/international/mefenamic-acid.html | title = International listings for mefenamic acid | access-date = 3 July 2015 }}</ref>

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.<ref>{{cite journal | title = Drugs for Osteoarthritis | journal = The Medical Letter | volume = 56 | issue = 1450 | pages = 80–84 | date = September 2014 | pmid = 25157683 }}</ref> By contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.<ref>{{cite web |url=https://www.medicinescomplete.com/mc/bnf/current/PHP6487-mefenamic-acid-non-proprietary.htm |title=Access leading drug and healthcare references |website=www.medicinescomplete.com |access-date=19 September 2014}}.</ref> In New Zealand, a weeks's supply of Ponstan costs NZ$9.08, around US$5.50. <ref>{{cite web |url=https://schedule.pharmac.govt.nz/ScheduleOnline.php?edition=&osq=Mefenamic+acid |website=schedule.pharmac.govt.nz |access-date=22 October 2024 |title=PHARMAC Schedule Online}}</ref>

==Research==
While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of [[Alzheimer's disease]]<ref>{{cite journal | vauthors = Joo Y, Kim HS, Woo RS, Park CH, Shin KY, Lee JP, Chang KA, Kim S, Suh YH | title = Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models | journal = Molecular Pharmacology | volume = 69 | issue = 1 | pages = 76–84 | date = January 2006 | pmid = 16223958 | doi = 10.1124/mol.105.015206 | s2cid = 20982844 }}</ref><ref>{{cite journal | vauthors = Daniels MJ, Rivers-Auty J, Schilling T, Spencer NG, Watremez W, Fasolino V, Booth SJ, White CS, Baldwin AG, Freeman S, Wong R, Latta C, Yu S, Jackson J, Fischer N, Koziel V, Pillot T, Bagnall J, Allan SM, Paszek P, Galea J, Harte MK, Eder C, Lawrence CB, Brough D | title = Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models | journal = Nature Communications | volume = 7 | pages = 12504 | date = August 2016 | pmid = 27509875 | pmc = 4987536 | doi = 10.1038/ncomms12504 | bibcode = 2016NatCo...712504D }}</ref> 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.<ref>{{cite journal | vauthors = Miguel-Álvarez M, Santos-Lozano A, Sanchis-Gomar F, Fiuza-Luces C, Pareja-Galeano H, Garatachea N, Lucia A | title = Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect | journal = Drugs & Aging | volume = 32 | issue = 2 | pages = 139–147 | date = February 2015 | pmid = 25644018 | doi = 10.1007/s40266-015-0239-z | s2cid = 35357112 }}</ref><ref>{{cite journal | vauthors = Jaturapatporn D, Isaac MG, McCleery J, Tabet N | title = Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD006378 | date = February 2012 | pmid = 22336816 | doi = 10.1002/14651858.CD006378.pub2 | pmc = 11337172 }}</ref><ref>{{cite journal | vauthors = Wang J, Tan L, Wang HF, Tan CC, Meng XF, Wang C, Tang SW, Yu JT | title = Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis | journal = Journal of Alzheimer's Disease | volume = 44 | issue = 2 | pages = 385–396 | year = 2015 | pmid = 25227314 | doi = 10.3233/JAD-141506 }}</ref> A small controlled study of 28 human subjects showed improved cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy.<ref>{{cite journal | vauthors = Melnikov V, Tiburcio-Jimenez D, Mendoza-Hernandez MA, Delgado-Enciso J, De-Leon-Zaragoza L, Guzman-Esquivel J, Rodriguez-Sanchez IP, Martinez-Fierro ML, Lara-Esqueda A, Delgado-Enciso OG, Jacinto-Cortes I, Zaizar-Fregoso SA, Paz-Michel BA, Murillo-Zamora E, Delgado-Enciso I, Galvan-Salazar HR | title = Improve cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy: additional beneficial effect found in a controlled clinical trial for prostate cancer therapy | journal = American Journal of Translational Research | volume = 13 | issue = 5 | pages = 4535–4543 | date = 2021 | pmid = 34150033 | pmc = 8205720 }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a681028.html | work = MedlinePlus Drug Information | title = Mefenamic Acid | access-date = 28 September 2005 | publisher = U.S. National Library of Medicine }}
* {{cite journal | vauthors = Page J, Henry D | title = Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem | journal = Archives of Internal Medicine | volume = 160 | issue = 6 | pages = 777–84 | date = March 2000 | pmid = 10737277 | doi = 10.1001/archinte.160.6.777 | doi-access = free }}
{{refend}}

{{Anti-inflammatory and antirheumatic products}}
{{Analgesics}}
{{GABAAR PAMs}}
{{Prostanoidergics}}
{{Ion channel modulators}}

[[Category:Nonsteroidal anti-inflammatory drugs]]
[[Category:Anthranilic acids]]
[[Category:GABAA receptor positive allosteric modulators]]