Chemistry:Tolfenamic acid

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Short description: Non-steroidal anti-inflammatory drug

Tolfenamic acid
Clinical data
Trade namesClotam, Clotan, Tufnil, Migea
AHFS/Drugs.comInternational Drug Names
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • EU: Rx-only [1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC14H12ClNO2
Molar mass261.71 g·mol−1
3D model (JSmol)
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Tolfenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs.[3] Like other members of the class, it is a COX inhibitor and prevents formation of prostaglandins.[4]

It is used in the UK as a treatment for migraine.[5][6] It is generally not available in the US.[4] It is available in some Asian, Latin American and European countries as a generic drug for humans and for animals.[7]

Medical uses

Tolfenamic acid finds utility in the prevention and treatment of conditions associated with pain and inflammation.[8][9] However, despite its efficacy when administered intramuscularly, subcutaneously, or orally,[10] TFA-based drugs have not yet gained approval in the United States and some other countries due to the significant number of reported side effects.[11][12]

Chemistry

Tolfenamic acid, belonging to the pharmacological group of fenamates, possesses a chemical structure typical of anthranilic acid derivatives. In this structure, one of the hydrogen atoms of the nitro group is substituted by a benzene ring featuring a methyl group and a chlorine atom at the ortho- and meta- positions, respectively.[13]

Nine forms of tolfenamic acid have been identified, some of which are determined by conformational states.[14][15][16] These polymorphic forms exhibit variations in the spatial arrangement within the unit cell and in the values of the C-N(H)-C-C angle.[16] This diversity in solid forms makes TFA an attractive candidate for modification and utilization in medical applications.

History

It was discovered by scientists at Gea Pharmaceutical Company in Denmark.[3]

Research

Tolfenamic acid demonstrates the ability to inhibit the growth of cancer cells in the pancreas, sigmoid colon, and rectum.[17]

References

  1. ↑ "Tolfenamic acid VMD". 5 December 2024. https://www.ema.europa.eu/en/medicines/veterinary/EPAR/tolfenamic-acid-vmd. 
  2. ↑ "Characterization of two polymorphic forms of tolfenamic acid, N-(2-methyl-3-chlorophenyl)anthranilic acid: their crystal structures and relative stabilities". J. Chem. Soc., Perkin Trans. 2 (10): 1443–1447. 1989. doi:10.1039/P29890001443. http://www.rsc.org/Publishing/Journals/P2/article.asp?. 
  3. ↑ 3.0 3.1 "Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent". European Journal of Clinical Pharmacology 19 (5): 359–365. 1981. doi:10.1007/bf00544587. PMID 7238564. 
  4. ↑ 4.0 4.1 NIH LiverTox Database Mefenamic Acid Last updated June 23, 2015. Page accessed July 3, 2015. Quote: "(fenamates generally not available in the United States, such as tolfenamic acid and flufenamic acid)"
  5. ↑ NHS Tolfenamic Acid (Tolfenamic acid 200mg tablets) Page accessed July 3, 2015
  6. ↑ "Virtual Medicinal Product (VMP) - Tolfenamic acid 200mg tablets - dm+d browser". https://dmd-browser.nhsbsa.nhs.uk/vmp/view/3703. 
  7. ↑ Drugs.com Drugs.com international listings for tolfenamic acid Page accessed July 3, 2015
  8. ↑ "Effect of tolfenamic acid in rheumatoid arthritis". Scandinavian Journal of Rheumatology 1 (2): 91–93. January 1972. doi:10.3109/03009747209103003. PMID 4572954. 
  9. ↑ "Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic acid". Frontiers in Bioscience 3 (2): 797–805. January 2011. doi:10.2741/s188. PMID 21196413. 
  10. ↑ "Pharmacokinetics and bioavailability of tolfenamic acid in sheep". Journal of Veterinary Pharmacology and Therapeutics 41 (6): 871–877. December 2018. doi:10.1111/jvp.12702. PMID 30084126. 
  11. ↑ "Tolfenamic acid versus propranolol in the prophylactic treatment of migraine". Acta Neurologica Scandinavica 89 (6): 446–450. June 1994. doi:10.1111/j.1600-0404.1994.tb02664.x. PMID 7976233. 
  12. ↑ "Tolfenamic acid: clinical experience in rheumatic diseases". Pharmacology & Toxicology 75 (s2): 64–65. October 1994. doi:10.1111/j.1600-0773.1994.tb02001.x. PMID 7816786. 
  13. ↑ "Polymer-induced heteronucleation of tolfenamic acid: structural investigation of a pentamorph". Journal of the American Chemical Society 131 (13): 4554–4555. April 2009. doi:10.1021/ja806289a. PMID 19334766. Bibcode: 2009JAChS.131.4554L. 
  14. ↑ "Conformational preferences of tolfenamic acid in DMSO-CO2 solvent system by 2D NOESY" (in en). Journal of Molecular Liquids 367. December 2022. doi:10.1016/j.molliq.2022.120481. 
  15. ↑ "Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid" (in en). Crystal Growth & Design 12 (8): 4283–4289. 2012-08-01. doi:10.1021/cg300812v. ISSN 1528-7483. Bibcode: 2012CrGrD..12.4283S. 
  16. ↑ 16.0 16.1 "Successful Computationally Directed Templating of Metastable Pharmaceutical Polymorphs" (in en). Crystal Growth & Design 18 (9): 5322–5331. 2018-09-05. doi:10.1021/acs.cgd.8b00765. ISSN 1528-7483. Bibcode: 2018CrGrD..18.5322C. 
  17. ↑ "Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway". Journal of Clinical Biochemistry and Nutrition 47 (1): 74–80. July 2010. doi:10.3164/jcbn.10-02. PMID 20664734.