Tolfenamic acid
{{Short description|Non-steroidal anti-inflammatory drug}}
{{Use dmy dates|date=December 2024}}
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{{Infobox drug
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| image = Tolfenamic acid FormulaV1.svg
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| tradename = Clotam, Clotan, Tufnil, Migea
| Drugs.com = {{drugs.com|international|tolfenamic-acid}}
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| routes_of_administration = By mouth
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| ATC_prefix = M01
| ATC_suffix = AG02
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| legal_AU = S4
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| legal_EU = Rx-only
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| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 13710-19-5
| PubChem = 610479
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB09216
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 530683
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 3G943U18KM
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| KEGG = D01183
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 32243
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 121626
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| IUPAC_name = 2-[(3-chloro-2-methylphenyl)amino]benzoic acid){{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 }}
| 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)
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YEZNLOUZAIOMLT-UHFFFAOYSA-N
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Tolfenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs.{{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 }} Like other members of the class, it is a COX inhibitor and prevents formation of prostaglandins.
It is used in the UK as a treatment for migraine.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{{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}} It is generally not available in the US.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)" It is available in some Asian, Latin American and European countries as a generic drug for humans and for animals.Drugs.com [https://www.drugs.com/international/tolfenamic-acid.html Drugs.com international listings for tolfenamic acid] Page accessed July 3, 2015
Medical uses
Tolfenamic acid finds utility in the prevention and treatment of conditions associated with pain and inflammation.{{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 }}{{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 }} However, despite its efficacy when administered intramuscularly, subcutaneously, or orally,{{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 }} 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.{{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 }}{{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 }}
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.{{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 }}
Nine forms of tolfenamic acid have been identified, some of which are determined by conformational states.{{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}}{{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}}{{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 }} 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. 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.
Research
Tolfenamic acid demonstrates the ability to inhibit the growth of cancer cells in the pancreas, sigmoid colon, and rectum.{{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 }}
References
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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:GABAA receptor positive allosteric modulators
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