View source for Tolfenamic acid

{{Short description|Non-steroidal anti-inflammatory drug}}
{{Use dmy dates|date=December 2024}}
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{{Infobox drug
| Verifiedfields = changed
| verifiedrevid = 470611500
| image = Tolfenamic acid FormulaV1.svg
| image_class = skin-invert-image
| width = 220
| alt = 

<!-- Clinical data -->
| pronounce         = 
| tradename =  Clotam, Clotan, Tufnil, Migea
| Drugs.com = {{drugs.com|international|tolfenamic-acid}}
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| DailyMedID        = <!-- DailyMed may use generic or brand name (generic name preferred) -->
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]]
| class             = 
| ATCvet            = 
| ATC_prefix = M01
| ATC_suffix = AG02
| ATC_supplemental  = 

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment  = 
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 -->
| legal_BR_comment  = 
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
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| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
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| legal_NZ          = <!-- Class A, B, C -->
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| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  = 
| legal_US          = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US_comment  = 
| legal_EU          = Rx-only
| legal_EU_comment  = <ref>{{cite web | title=Tolfenamic acid VMD | website=European Medicines Agency (EMA) | date=5 December 2024 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/tolfenamic-acid-vmd | access-date=6 December 2024}}</ref>
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  = 
| legal_status      = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
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<!-- Identifiers -->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 13710-19-5
| PubChem = 610479
| IUPHAR_ligand     = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank          = DB09216
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 530683
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 3G943U18KM
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01183
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 32243
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 121626
| NIAID_ChemDB      = 
| PDB_ligand        = 
| synonyms          = 

<!-- Chemical and physical data -->
| IUPAC_name = 2-[(3-chloro-2-methylphenyl)amino]benzoic acid)<ref name="Andersen">{{cite journal | vauthors = Andersen KV, Larsen S, Alhede B, Gelting N, Buchardt O | url = http://www.rsc.org/Publishing/Journals/P2/article.asp? | title = Characterization of two polymorphic forms of tolfenamic acid, N-(2-methyl-3-chlorophenyl)anthranilic acid: their crystal structures and relative stabilities | journal = J. Chem. Soc., Perkin Trans. 2 | year = 1989 | issue = 10 | pages = 1443–1447 | doi = 10.1039/P29890001443| url-access = subscription }}</ref>
| C=14 | H=12 | Cl=1 | N=1 | O=2
| SMILES = Clc2cccc(Nc1ccccc1C(=O)O)c2C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChI_comment  = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YEZNLOUZAIOMLT-UHFFFAOYSA-N
| density           = 
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| specific_rotation = 
}}

'''Tolfenamic acid''' is a member of the [[Nonsteroidal anti-inflammatory drug#Anthranilic acid derivatives (Fenamates)|anthranilic acid derivatives]] (or fenamate) class of [[NSAID]] drugs.<ref name=":0">{{cite journal | vauthors = Pentikäinen PJ, Neuvonen PJ, Backman C | title = Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent | journal = European Journal of Clinical Pharmacology | volume = 19 | issue = 5 | pages = 359–365 | year = 1981 | pmid = 7238564 | doi = 10.1007/bf00544587 | s2cid = 9428076 }}</ref> Like other members of the class, it is a [[COX]] inhibitor and prevents formation of [[prostaglandins]].<ref name=LiverTox/>

It is used in the UK as a treatment for [[migraine]].<ref>NHS [https://web.archive.org/web/20111129071132/http://www.nhs.uk/medicine-guides/pages/MedicineOverview.aspx?condition=Migraine%20Headache&medicine=Tolfenamic%20Acid&preparation= Tolfenamic Acid (Tolfenamic acid 200mg tablets)] Page accessed July 3, 2015</ref><ref>{{Cite web |title=Virtual Medicinal Product (VMP) - Tolfenamic acid 200mg tablets - dm+d browser |url=https://dmd-browser.nhsbsa.nhs.uk/vmp/view/3703 |access-date=2024-04-23 |website=dmd-browser.nhsbsa.nhs.uk}}</ref> It is generally not available in the US.<ref name=LiverTox>NIH LiverTox Database [http://livertox.nih.gov/MefenamicAcid.htm 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)"</ref> It is available in some Asian, Latin American and European countries as a [[generic drug]] for humans and for animals.<ref>Drugs.com [https://www.drugs.com/international/tolfenamic-acid.html Drugs.com international listings for tolfenamic acid] Page accessed July 3, 2015</ref>

== Medical uses ==
Tolfenamic acid finds utility in the prevention and treatment of conditions associated with pain and inflammation.<ref>{{cite journal | vauthors = Kajander A, Laine V, Gothoni G | title = Effect of tolfenamic acid in rheumatoid arthritis | journal = Scandinavian Journal of Rheumatology | volume = 1 | issue = 2 | pages = 91–93 | date = January 1972 | pmid = 4572954 | doi = 10.3109/03009747209103003 }}</ref><ref>{{cite journal | vauthors = Basha R, Baker CH, Sankpal UT, Ahmad S, Safe S, Abbruzzese JL, Abdelrahim M | title = Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic acid | journal = Frontiers in Bioscience | volume = 3 | issue = 2 | pages = 797–805 | date = January 2011 | pmid = 21196413 | doi = 10.2741/s188 }}</ref> However, despite its efficacy when administered intramuscularly, subcutaneously, or orally,<ref>{{cite journal | vauthors = Corum O, Corum DD, Er A, Yildiz R, Uney K | title = Pharmacokinetics and bioavailability of tolfenamic acid in sheep | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 41 | issue = 6 | pages = 871–877 | date = December 2018 | pmid = 30084126 | doi = 10.1111/jvp.12702 | s2cid = 51930602 }}</ref> 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.<ref>{{cite journal | vauthors = Kjaersgård Rasmussen MJ, Holt Larsen B, Borg L, Soelberg Sørensen P, Hansen PE | title = Tolfenamic acid versus propranolol in the prophylactic treatment of migraine | journal = Acta Neurologica Scandinavica | volume = 89 | issue = 6 | pages = 446–450 | date = June 1994 | pmid = 7976233 | doi = 10.1111/j.1600-0404.1994.tb02664.x | s2cid = 12334561 }}</ref><ref>{{cite journal | vauthors = Isomäki H | title = Tolfenamic acid: clinical experience in rheumatic diseases | journal = Pharmacology & Toxicology | volume = 75 | issue = s2 | pages = 64–65 | date = October 1994 | pmid = 7816786 | doi = 10.1111/j.1600-0773.1994.tb02001.x }}</ref>

== 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.<ref>{{cite journal |vauthors=López-Mejías V, Kampf JW, Matzger AJ |date=April 2009 |title=Polymer-induced heteronucleation of tolfenamic acid: structural investigation of a pentamorph |journal=Journal of the American Chemical Society |volume=131 |issue=13 |pages=4554–4555 |doi=10.1021/ja806289a |pmc=2729806 |pmid=19334766|bibcode=2009JAChS.131.4554L }}</ref>

Nine forms of tolfenamic acid have been identified, some of which are determined by conformational states.<ref>{{Cite journal |vauthors=Belov KV, Dyshin AA, Krestyaninov MA, Efimov SV, Khodov IA, Kiselev MG |date=December 2022 |title=Conformational preferences of tolfenamic acid in DMSO-CO2 solvent system by 2D NOESY |journal=Journal of Molecular Liquids |language=en |volume=367 |pages=120481 |doi=10.1016/j.molliq.2022.120481 |s2cid=252630985}}</ref><ref>{{Cite journal |vauthors=SeethaLekshmi S, Guru Row TN |date=2012-08-01 |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 |bibcode=2012CrGrD..12.4283S |issn=1528-7483}}</ref><ref name="Case_2018">{{Cite journal |vauthors=Case DH, Srirambhatla VK, Guo R, Watson RE, Price LS, Polyzois H, Cockcroft JK, Florence AJ, Tocher DA, Price SL |date=2018-09-05 |title=Successful Computationally Directed Templating of Metastable Pharmaceutical Polymorphs |journal=Crystal Growth & Design |language=en |volume=18 |issue=9 |pages=5322–5331 |doi=10.1021/acs.cgd.8b00765 |bibcode=2018CrGrD..18.5322C |issn=1528-7483|doi-access=free }}</ref> 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.<ref name = "Case_2018" /> 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]].<ref name=":0" />

== Research ==
Tolfenamic acid demonstrates the ability to inhibit the growth of cancer cells in the pancreas, sigmoid colon, and rectum.<ref>{{cite journal | vauthors = Kim JH, Jung JY, Shim JH, Kim J, Choi KH, Shin JA, Choi ES, Lee SO, Chintharlapalli S, Kwon KH, Leem DH, Cho NP, Cho SD | title = Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway | journal = Journal of Clinical Biochemistry and Nutrition | volume = 47 | issue = 1 | pages = 74–80 | date = July 2010 | pmid = 20664734 | pmc = 2901767 | doi = 10.3164/jcbn.10-02 }}</ref>

== References ==
{{reflist}}

== External links ==
* [http://www.diseasesdatabase.com/ddb31603.htm Tolfenamic acid information] (Diseases Database)

{{Anti-inflammatory and antirheumatic products}}
{{GABAAR PAMs}}
{{Prostanoidergics}}
{{Serotonergics}}
{{Ion channel modulators}}
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[[Category:Nonsteroidal anti-inflammatory drugs]]
[[Category:Antipyretics]]
[[Category:Chloroarenes]]
[[Category:Anthranilic acids]]
[[Category:GABAA receptor positive allosteric modulators]]


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