Mefenamic acid

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Mefenamic acid
Mefenamic acid2DACS.svg
Mefenamic acid3Dan.gif
Systematic (IUPAC) name
2-(2,3-dimethylphenyl)aminobenzoic acid
Clinical data
Trade names Ponstel, Ponstan
AHFS/Drugs.com Monograph
MedlinePlus a681028
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration
Oral
Legal status
Legal status
  • AU: S2 (Pharmacy only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability 90%
Protein binding 90%
Metabolism Hepatic (CYP2C9)
Biological half-life 2 hours
Excretion Urine (66%), faeces (20-25%)
Identifiers
CAS Number 61-68-7 YesY
ATC code M01AG01 (WHO)
PubChem CID 4044
IUPHAR/BPS 2593
DrugBank DB00784 YesY
ChemSpider 3904 YesY
UNII 367589PJ2C YesY
KEGG D00151 YesY
ChEBI CHEBI:6717 N
ChEMBL CHEMBL686 YesY
Chemical data
Formula C15H15NO2
Molar mass 241.285 g/mol
 NYesY (what is this?)  (verify)

Mefenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs, and is used to treat mild to moderate pain, including menstrual pain, and is sometimes used to prevent migraines associated with menstruation.[1][2] It is not widely used due to its side effects.[3][4]:334

Its name derives from its systematic name, dimethylphenylaminobenzoic acid. It was discovered and brought to market by Parke-Davis in the 1960s under brandnames Ponstan, Ponstan Forte, Ponalar, Ponstyl, and Ponstel. It became generic in the 1980s and is available worldwide under many brand names.[5] As of 2015 the cost for a typical course of medication in the United States is more than 200 USD.[6]

Medical use[edit]

Mefenamic acid is used to treat moderate pain and menstrual pain.[1] It is not widely used.[3][4]:334

There is evidence that supports the use of mefenamic acid for perimenstrual migraine headache prophylaxis, with treatment starting 2 days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the duration of menstruation.[2]

Side effects[edit]

Mefenamic acid is recommended to be taken with food.[7]

Known mild side effects of mefenamic acid include headaches, nervousness and vomiting. Serious side effects may include diarrhea, hematemesis (vomiting blood), haematuria (blood in urine), blurred vision, skin rash, itching and swelling, sore throat and fever.[4]:334 It has been associated with acute liver damage.[3]

In 2008 the US label was updated with a warning concerning a risk of premature closure of the ductus arteriosus in pregnancy.[8]

Mechanism of action[edit]

Like other members of the anthranilic acid derivatives (or fenamate) class of NSAID drugs, it inhibits both isoforms of COX and prevents formation of prostaglandins.[3][9]

Synthesis[edit]

Analogous to fenamic acid, this compound may be synthesized from 2-chlorobenzoic acid and 2,3-dimethylaniline.[10]

History[edit]

Scientists led by Claude Winder from Parke-Davis invented mefenamic acid in 1961, along with fellow members of the class of anthranilic acid derivatives, flufenamic acid in 1963 and meclofenamate sodium in 1964.[11]:718 U.S. Patent 3,138,636 on the drug was issued in 1964.[12][13]:918–919

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".[3][13]:918–919

Availability and Pricing[edit]

Mefenamic acid is generic and is available worldwide under many brand names.[5]

In the USA, 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.[14] In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.[15] In the Philippines, 10 tablets of 500 mg generic mefenamic acid cost PHP39.00 (or the equivalent of $0.88USD)as of October 25, 2014.

Research[edit]

While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of Alzheimer's disease[16][17] there is no good evidence that mefenamic acid or other NSAIDs can treat or prevent Alzheimer's in humans; clinical trials of NSAIDs for treatment of Alzheimer's have found more harm than benefit.[18][19][20]

See also[edit]

References[edit]

  1. ^ a b FDA Ponstel Label Updated February 19, 2008
  2. ^ a b Pringsheim, T.; Davenport, W. J.; Dodick, D. (2008). "Acute Treatment and Prevention of Menstrually Related Migraine Headache: Evidence-Based Review". Neurology. 70 (17): 1555–1563. doi:10.1212/01.wnl.0000310638.54698.36. PMID 18427072. 
  3. ^ a b c d e NIH LiverTox Database Mefenamic Acid Last updated June 23, 2015. Page accessed July 3, 2015
  4. ^ a b c Jeffrey K. Aronson. Meyler's Side Effects of Analgesics and Anti-inflammatory Drugs. Elsevier, 2009 ISBN 9780080932941
  5. ^ a b Drugs.com drugs.com international listings for mefenamic acid Page accessed July 3, 2015
  6. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. X. ISBN 9781284057560. 
  7. ^ "Side effects for Mefenamic Acid". Medline Plus. National Institutes of Health. 
  8. ^ FDA March 2008 FDA advisory
  9. ^ Prusakiewicz JJ et al. Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid. Biochemistry. 2009 Aug 11;48(31):7353-5 PMID 19603831 PMC 2720641
  10. ^ Trinus, F. P.; Mokhort, N. A.; Yagupol'skii, L. M.; Fadeicheva, A. G.; Danilenko, V. S.; Ryabukha, T. K.; Fialkov, Yu. A.; Kirichek, L. M.; Endel'man, É. S.; Get'man, G. A. (1977). "Mefenamic acid — A Nonsteroid Antiinflammatory Agent". Pharmaceutical Chemistry Journal. 11 (12): 1706–1711. doi:10.1007/BF00778304. 
  11. ^ Whitehouse M. Drugs to Treat Inflammation: A Historical Overview. pp 707-729 in Frontiers in Medicinal Chemistry , Volume 4. Eds Rahman A, et al. Bentham Science Publishers, 2009 ISBN 9781608052073
  12. ^ US Patent 3,138,636
  13. ^ a b Marshall Sittig Pharmaceutical Manufacturing Encyclopedia Volume 1 A-K Second Edition, Reprint Edition. Noyes Publications, 1988
  14. ^ Drugs for Osteoarthritis. The Medical Letter, 56(1450):80-84, September 2014
  15. ^ https://www.medicinescomplete.com/mc/bnf/current/PHP6487-mefenamic-acid-non-proprietary.htm accessed 19th sept 2014
  16. ^ Joo Y et al. Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models. Mol Pharmacol. 2006 Jan;69(1):76-84. PMID 16223958
  17. ^ Daniels MJ et al Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models. Nat Commun. 2016 Aug 11;7:12504. PMID 27509875
  18. ^ Miguel-Álvarez M et al Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect. Drugs Aging. 2015 Feb;32(2):139-47. Review. PMID 25644018
  19. ^ Jaturapatporn D et al. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD006378. PMID 22336816
  20. ^ Wang J et al Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis. J Alzheimers Dis. 2015;44(2):385-96. PMID 25227314

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