Tolfenamic acid

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Tolfenamic acid
Tolfenamic acid FormulaV1.svg
Clinical data
Trade names Clotam, Clotan, Tufnil
AHFS/Drugs.com International Drug Names
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
Identifiers
  • 2-[(3-chloro-2-methylphenyl)amino]benzoic acid) [1]
CAS Number
PubChem CID
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 (Clotam, Tufnil, TFA) is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs. [2] Like other members of the class, it is a COX inhibitor and prevents formation of prostaglandins. [3]

Contents

It is used in the UK as a treatment for migraine. [4] [5] It is generally not available in the US. [3] It is available in some Asian, Latin American and European countries as a generic drug for humans and for animals. [6]

Medical uses

TFA, like other non-steroidal anti-inflammatory drugs (NSAIDs), finds utility in the prevention and treatment of conditions associated with pain and inflammation. [7] [8] However, despite its efficacy when administered intramuscularly, subcutaneously, or orally, [9] 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. [10] [11]

Nevertheless, TFA exhibits promise in medical practice, demonstrating the ability to inhibit the growth of cancer cells in the pancreas, sigmoid colon, and rectum. [12] Further research and development may unveil its potential for therapeutic applications in the future.

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]

Currently, nine forms of TFA 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 Medica Pharmaceutical Company in Finland. [2]

Related Research Articles

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<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

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Anthranilic acid is an aromatic acid with the formula C6H4(NH2)(CO2H) and has a sweetish taste. The molecule consists of a benzene ring, ortho-substituted with a carboxylic acid and an amine. As a result of containing both acidic and basic functional groups, the compound is amphoteric. Anthranilic acid is a white solid when pure, although commercial samples may appear yellow. The anion [C6H4(NH2)(CO2)]−, obtained by the deprotonation of anthranilic acid, is called anthranilate. Anthranilic acid was once thought to be a vitamin and was referred to as vitamin L1 in that context, but it is now known to be non-essential in human nutrition.

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<span class="mw-page-title-main">Flufenamic acid</span> Chemical compound

Flufenamic acid (FFA) is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs). Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins. FFA is known to bind to and reduce the activity of prostaglandin F synthase and activate TRPC6.

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References

  1. ↑ 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.
  2. 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.
  3. 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)"
  4. ↑ NHS Tolfenamic Acid (Tolfenamic acid 200mg tablets) Page accessed July 3, 2015
  5. ↑ "Virtual Medicinal Product (VMP) - Tolfenamic acid 200mg tablets - dm+d browser". dmd-browser.nhsbsa.nhs.uk. Retrieved 2024-04-23.
  6. ↑ Drugs.com Drugs.com international listings for tolfenamic acid Page accessed July 3, 2015
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  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. 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 (2012-08-01). "Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid". Crystal Growth & Design. 12 (8): 4283–4289. doi:10.1021/cg300812v. ISSN   1528-7483.
  16. 1 2 Case DH, Srirambhatla VK, Guo R, Watson RE, Price LS, Polyzois H, et al. (2018-09-05). "Successful Computationally Directed Templating of Metastable Pharmaceutical Polymorphs". Crystal Growth & Design. 18 (9): 5322–5331. doi:10.1021/acs.cgd.8b00765. ISSN   1528-7483.
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