Tolfenamic acid

Last updated

Tolfenamic acid
Tolfenamic acid FormulaV1.svg
Clinical data
Trade names Clotam, Clotan, Tufnil, Migea
AHFS/Drugs.com International Drug Names
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • EU:Rx-only [1]
Identifiers
  • 2-[(3-chloro-2-methylphenyl)amino]benzoic acid) [2]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.033.862 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H12ClNO2
Molar mass 261.71 g·mol−1
3D model (JSmol)
  • Clc2cccc(Nc1ccccc1C(=O)O)c2C
  • InChI=1S/C14H12ClNO2/c1-9-11(15)6-4-8-12(9)16-13-7-3-2-5-10(13)14(17)18/h2-8,16H,1H3,(H,17,18) Yes check.svgY
  • Key:YEZNLOUZAIOMLT-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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]

Contents

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". European Medicines Agency (EMA). 5 December 2024. Retrieved 6 December 2024.
  2. ↑ Andersen KV, Larsen S, Alhede B, Gelting N, Buchardt O (1989). "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. doi:10.1039/P29890001443.
  3. 1 2 Pentikäinen PJ, Neuvonen PJ, Backman C (1981). "Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent". European Journal of Clinical Pharmacology. 19 (5): 359–365. doi:10.1007/bf00544587. PMID   7238564. S2CID   9428076.
  4. 1 2 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". dmd-browser.nhsbsa.nhs.uk. Retrieved 23 April 2024.
  7. ↑ Drugs.com Drugs.com international listings for tolfenamic acid Page accessed July 3, 2015
  8. ↑ Kajander A, Laine V, Gothoni G (January 1972). "Effect of tolfenamic acid in rheumatoid arthritis". Scandinavian Journal of Rheumatology. 1 (2): 91–93. doi:10.3109/03009747209103003. PMID   4572954.
  9. ↑ Basha R, Baker CH, Sankpal UT, Ahmad S, Safe S, Abbruzzese JL, et al. (January 2011). "Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic acid". Frontiers in Bioscience. 3 (2): 797–805. doi:10.2741/s188. PMID   21196413.
  10. ↑ Corum O, Corum DD, Er A, Yildiz R, Uney K (December 2018). "Pharmacokinetics and bioavailability of tolfenamic acid in sheep". Journal of Veterinary Pharmacology and Therapeutics. 41 (6): 871–877. doi:10.1111/jvp.12702. PMID   30084126. S2CID   51930602.
  11. ↑ Kjaersgård Rasmussen MJ, Holt Larsen B, Borg L, Soelberg Sørensen P, Hansen PE (June 1994). "Tolfenamic acid versus propranolol in the prophylactic treatment of migraine". Acta Neurologica Scandinavica. 89 (6): 446–450. doi:10.1111/j.1600-0404.1994.tb02664.x. PMID   7976233. S2CID   12334561.
  12. ↑ Isomäki H (October 1994). "Tolfenamic acid: clinical experience in rheumatic diseases". Pharmacology & Toxicology. 75 (s2): 64–65. doi:10.1111/j.1600-0773.1994.tb02001.x. PMID   7816786.
  13. ↑ López-Mejías V, Kampf JW, Matzger AJ (April 2009). "Polymer-induced heteronucleation of tolfenamic acid: structural investigation of a pentamorph". Journal of the American Chemical Society. 131 (13): 4554–4555. Bibcode:2009JAChS.131.4554L. doi:10.1021/ja806289a. PMC   2729806 . PMID   19334766.
  14. ↑ Belov KV, Dyshin AA, Krestyaninov MA, Efimov SV, Khodov IA, Kiselev MG (December 2022). "Conformational preferences of tolfenamic acid in DMSO-CO2 solvent system by 2D NOESY". Journal of Molecular Liquids. 367: 120481. doi:10.1016/j.molliq.2022.120481. S2CID   252630985.
  15. ↑ SeethaLekshmi S, Guru Row TN (1 August 2012). "Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid". Crystal Growth & Design. 12 (8): 4283–4289. Bibcode:2012CrGrD..12.4283S. doi:10.1021/cg300812v. ISSN   1528-7483.
  16. 1 2 Case DH, Srirambhatla VK, Guo R, Watson RE, Price LS, Polyzois H, et al. (5 September 2018). "Successful Computationally Directed Templating of Metastable Pharmaceutical Polymorphs". Crystal Growth & Design. 18 (9): 5322–5331. Bibcode:2018CrGrD..18.5322C. doi: 10.1021/acs.cgd.8b00765 . ISSN   1528-7483.
  17. ↑ Kim JH, Jung JY, Shim JH, Kim J, Choi KH, Shin JA, et al. (July 2010). "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. doi:10.3164/jcbn.10-02. PMC   2901767 . PMID   20664734.


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