Flufenamic acid

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Flufenamic acid
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth, topical
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
Pharmacokinetic data
Protein bindingextensively
MetabolismHydroxylation, glucuronidation
Elimination half-life~3 h
Excretion50% urine, 36% feces
Identifiers
  • 2-{[3-(Trifluoromethyl)phenyl]amino}benzoic acid
JSmol)
Melting point124 to 125 °C (255 to 257 °F) resolidification and remelting at 134°C to 136°C
Solubility in waterPractically insoluble in water; soluble in ethanol, chloroform and diethyl ether mg/mL (20 °C)
  • FC(F)(F)c1cc(ccc1)Nc2ccccc2C(=O)O
  • InChI=1S/C14H10F3NO2/c15-14(16,17)9-4-3-5-10(8-9)18-12-7-2-1-6-11(12)13(19)20/h1-8,18H,(H,19,20) checkY
  • Key:LPEPZBJOKDYZAD-UHFFFAOYSA-N checkY
  (verify)

Flufenamic acid (FFA) is a member of the

prostaglandins.[2] FFA is known to bind to and reduce the activity of prostaglandin F synthase and activate TRPC6.[3]

Scientists led by Claude Winder from Parke-Davis invented FFA in 1963, along with fellow members of the class, mefenamic acid in 1961 and meclofenamic acid in 1964.[1]: 718 

Although flufenamic acid was at one time informally referred to as "Fluffy" (see history cache), this pet name could also refer to flufenoxine.

Structure

Flufenamic acid is a highly polymorphic drug molecule with multiple structurally characterized polymorphic modifications.[4] It has a unique chemical structure and stands out among fenamates.[5] Nowadays, eight polymorphic forms are known that are determined by different conformers,[6][7] which makes flufenamic acid unique among other low-molecular medicinal compounds.[8][9] A fundamental feature of the structure of flufenamic acid, which has generated significant interest in the design and development of drugs,[10] is the presence of a trifluoromethyl group. Compounds with fluorine-containing substituents are known to have promising chemical and biological properties,[11][12] since such groups often improve the pharmacokinetics and bioavailability of drugs.[13] Studies have shown the promise of repositioning flufenamic acid and the use of drugs based on it in the treatment of Bartter syndrome.

Medical uses

Until recently, FFA was actively used in medical practice as an analgesic with anti-inflammatory and antipyretic effects.[14] FFA has been proven effective in treating rheumatoid arthritis, osteoarthritis and other inflammation-related diseases.[15] However, despite this, the use of FFA in the United States and other countries [16] is limited since the compound causes frequent side effects. The rate of gastrointestinal side effects can be as high as 60%,[17] manifested as at least one of the following: dyspepsia, nausea, abdominal pain and discomfort, constipation, diarrhoea, flatulence, indigestion, epigastric distress, stomatitits and anorexia.[17] Besides gastrointestinal side effects, the drug can cause headache, dizziness and peripheral oedema.[17]

Side effects

It is not widely used in humans as it has a high rate (30–60%) of gastrointestinal side effects.[18] It is generally not available in the US.[2] It is available in some Asian and European countries as a generic drug.[19]

References

  1. ^
    PMID 16378496
    .
  2. ^
    PMID 31643176
    . Retrieved July 3, 2015. (fenamates generally not available in the United States, such as tolfenamic acid and flufenamic acid)
  3. ^ "Chemical–Gene Interaction Query: Flufenamic Acid (Homo sapiens)". Comparative Toxicogenomics Database. North Carolina State University. Retrieved July 4, 2015.
  4. S2CID 100245760
    .
  5. S2CID 218479815
    .
  6. PMID 36837153
    .
  7. PMID 37367811
    .
  8. doi:10.1016/j.molstruc.2014.02.001
    .
  9. PMID 22690822
    .
  10. S2CID 4690397
    .
  11. PMID 23614876
    .
  12. hdl:2164/2557
    .
  13. PMID 26372652
    .
  14. PMID 28185907
    .
  15. S2CID 209499101
    .
  16. PMID 36015147
    .
  17. ^
    ISBN 978-0-444-53716-4
    .
  18. ISBN 978-0-08-093294-1
    .
  19. ^ "International listings for flufenamic acid". Drugs.com. Archived from the original on June 30, 2019. Retrieved July 3, 2015.