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 Medica Pharmaceutical Company in Finland. [3]

Research

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

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Drugs used to achieve relief from pain

An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Ibuprofen</span> Medication treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be taken orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Naproxen</span> Nonsteroidal anti-inflammatory drug (NSAID) used to treat pain

Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, and inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulations. Onset of effects is within an hour and lasts for up to twelve hours. Naproxen is also available in salt form, naproxen sodium, which has better solubility when taken orally.

<span class="mw-page-title-main">Imidazopyridine</span> Class of compounds

An imidazopyridine is a nitrogen containing heterocycle that is also a class of drugs that contain this same chemical substructure. In general, they are GABAA receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to benzodiazepines. As such, GABAA-agonizing imidazopyridines, pyrazolopyrimidines, and cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include:

<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by CYP3A4 gene. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

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

Mefenamic acid is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to moderate pain.

<span class="mw-page-title-main">Tiagabine</span> Anticonvulsant medication

Tiagabine is an anticonvulsant medication produced by Cephalon that is used in the treatment of epilepsy. The drug is also used off-label in the treatment of anxiety disorders and panic disorder.

<span class="mw-page-title-main">Diflunisal</span> NSAID analgesic and anti-inflammatory drug

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971, as MK647, after showing promise in a research project studying more potent chemical analogs of aspirin. It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is classed as a nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.

In crystallography, polymorphism is the phenomenon where a compound or element can crystallize into more than one crystal structure.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

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

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.

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

Meclofenamic acid is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs) and was approved by the US FDA in 1980. Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins.

<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.

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

Dexibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It is the active dextrorotatory enantiomer of ibuprofen. Most ibuprofen formulations contain a racemic mixture of both isomers.

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

Fenamic acid is an organic compound, which, especially in its ester form, is called fenamate. serves as a parent structure for several nonsteroidal anti-inflammatory drugs (NSAIDs), including mefenamic acid, tolfenamic acid, flufenamic acid, and meclofenamic acid. These drugs are commonly referred to as "anthranilic acid derivatives" or "fenamates" because fenamic acid is a derivative of anthranilic acid.

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

Ciclazindol (WY-23409) is an antidepressant and anorectic drug of the tetracyclic chemical class that was developed in the mid to late 1970s, but was never marketed. It acts as a norepinephrine reuptake inhibitor, and to a lesser extent as a dopamine reuptake inhibitor. Ciclazindol has no effects on the SERT, 5-HT receptors, mACh receptors, or α-adrenergic receptors, and has only weak affinity for the H1 receptor. As suggested by its local anesthetic properties, ciclazindol may also inhibit sodium channels. It is known to block potassium channels as well.

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They are selective 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D) agonists. Migraine is a complex disease which affects about 15% of the population and can be highly disabling. Triptans have advantages over ergotamine and dihydroergotamine, such as selective pharmacology, well established safety record and evidence-based prescribing instructions. Triptans are therefore often preferred treatment in migraine.

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<span class="mw-page-title-main">Lysine acetylsalicylate</span> Chemical compound

Lysine acetylsalicylate, also known as aspirin DL-lysine or lysine aspirin, is a more soluble form of acetylsalicylic acid (aspirin). As with aspirin itself, it is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory, antithrombotic and antipyretic properties. It is composed of the ammonium form of the amino acid lysine paired with the conjugate base of aspirin.

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. 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. 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. 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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