Flufenamic acid

Description

Flufenamic acid (FFA), namely N-(alpha,alpha,alpha-trifluorom-tolyl) anthranilic acid (CI-440), is an aromatic amino acid consisting of anthranilic acid carrying an N-(trifluoromethyl)phenyl substituent. It is an effective drug in the treatment of special types of migraine. Its anti-inflammatory and analgesic effects were recognized in the 1960s (Winder et al., 1963) and thus FFA is included in the family of non-steroidal anti-inflammatory drugs (NSAIDs) with mefenamic, meclofenamic (MFA) and niflumic acids (NA). Anti-inflammatory actions occur mainly through reduction of prostaglandin synthesis from arachidonic acid by inhibiting the cyclo-oxygenases.

Chemical properties

Fluomic acid is a Pale-Yellow or light yellow-green crystal or crystalline powder with bitter taste. It is almost insoluble in water and can be dissolved in 50% ethanol. It is a non-hormonal anti-inflammatory and analgesic drug. It was prepared by photolysis of the corresponding benzotriazinone.

Originator

Flufenamic acid,AroKor Holdings Inc.

The Uses of Flufenamic acid

Flufenamic acid is used for moderate pain and dysmenorrhea, but it should not be used for more than 1 week due to the possibility of nephrotoxicity, gastrointestinal toxicity, and anemia. It is frequently used in combination with the anticoagulant warfarin, the effect of which is strengthened when combined with flufenamic acid.

The Uses of Flufenamic acid

An NSAID found to be a reversible gap junction blocker

What are the applications of Application

Flufenamic acid is a reversible gap junction blocker

Background

An anthranilic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. It is used in musculoskeletal and joint disorders and administered by mouth and topically. (From Martindale, The Extra Pharmacopoeia, 30th ed, p16)

Definition

ChEBI: flufenamic acid is an aromatic amino acid consisting of anthranilic acid carrying an N-(trifluoromethyl)phenyl substituent. An analgesic and anti-inflammatory, it is used in rheumatic disorders. It has a role as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, a non-steroidal anti-inflammatory drug, a non-narcotic analgesic and an antipyretic. It is an aromatic amino acid and an organofluorine compound. It derives from a diphenylamine, an anthranilic acid and a (trifluoromethyl)benzene. It is a conjugate acid of a flufenamate.

Manufacturing Process

A mixture 31.3 g of o-chlorobenzoic acid, 32.2 g of trifluoromethyl-maminobenzene, 3 g of copper powder, 13.8 g of waterless potassium carbonate and 100 ml amyl alcohol was refluxed for 4 hours. To the cooled mixture was added 25 ml of 10 N solution NaOH and the mixture was concentrated and filtrated. Addition to the filtrate hydrochloric acid and water give a sediment of 2-((3-trifluromethyl)phenyl)aminobenzoic acid. After recrystallization from hexane 2-((3-trifluromethyl)phenyl)aminobenzoic acid have melting point 134-136°C.

brand name

Arlef (Parke-Davis, Sankyo, Japan), Ansatin (Ono, Japan), Felunamin (Hokuriko, Japan), Romafen (Biofarma, Turkey).

Therapeutic Function

Antiinflammatory, Antirheumatic

Biological Activity

Flufenamic acid is a nonsteroidal anti-inflammatory drug (NSAID). Inhibits calcium-activated chloride channels (CaCCs). Also increases currents through TRPC6 channels and inhibits currents through TRPC3 and TRPC7 channels.

Mechanism of action

In addition to COX inhibition flufenamate like other fenamates modifies several ion channel functions, e.g., inhibition of nonselective cation conductance, calcium-activated chloride channels, voltage-gated calcium channels and potassium channels and induces blocking of gap junctions. The relevance of these activities for the analgesic and anti-inflammatory potential of fenamates is unknown.

Clinical Use

Flufenamate is a nonsteroidal anti-inflammatory drug used for the treatment of mild to moderate pain of musculoskeletal, joint or soft-tissue origin. It was marketed in a variety of topical formulations alone or in combination with other ingredients.

Safety

Flufenamic acid is used at 600 – 800 mg/d to provide a beneficial therapeutic effect in chronic polyarthritis. The adverse effects most often encountered are gastrointestinal disturbances.

Synthesis

Flufenamic acid, N-(|á,|á,|á-trifluoro-m-tolyl)anthranylic acid (3.2.18), is synthesized by the reaction of 2-chlorobenzoic acid with 3-trifluoromethylaniline in the presence of potassium carbonate and copper filings [78,79].

Metabolism

Not Available

storage

Store at RT