Meclofenamic acid is sold under the trade name "Arquel" for use in horses, and is administered as an oral granual form at a dose of 2.2 mg/kg/day. It has a relatively slow onset of action, taking 36–48 hours for full effect, and is most useful for treatment of chronic musculoskeletal disease. It has been found to be beneficial for the treatment of navicular syndrome, laminitis, and osteoarthritis, in some cases having a more profound effect than the commonly-used NSAID phenylbutazone. However, due to cost, it is not routinely used in practice. Toxicity due to excessive dosage is similar to that of phenylbutazone, including depression, anorexia, weight loss, edema, diarrhea, oral ulceration, and decreased hematocrit.
N-aryl anthranilic acids are frequently found to have antiinflammatory activity and have been studied extensively to maximize potency and decreaase side effects (gastric irritation, ulcers, etc.). These compounds are often synthesized by reacting an ortho-halobenzoate salt with a suitably substituted aniline. This procedure failed because of steric hindrance, in attempting to synthesized meclofenamic acid. The successful synthesis begins by treating 2-methyl-4-hydroxy acetophenone (4) with NaOCl, which both ortho-chlorinates adjacent to the phenolic OH and effects a haloform reaction. Decarboxylation leads to the chlorinated meta cresol (5). When 5 is converted to its sodium salt with NaH in DMF and then treated with 2,4-dichloroquinazoline (6), two molecules of the phenol react with the heterocycle to give the nucleophilic aromatic substitution product (7). When heated, 7 undergoes an O to N-aryl rearrangement (Chapman rearrangement) to give 8. Upon saponification, carbon dioxide and 2,6-dichloro-3-methylaniline (1) are lost and meclofenamic acid (3) results.
^NIH LiverTox Database Mefenamic Acid Last updated June 23, 2015. Page accessed July 3, 2015
^Whitehouse M. Drugs to Treat Inflammation: A Historical Overview. pp 707-729 in Frontiers in Medicinal Chemistry , Volume 4. Eds Rahman A, et al. Bentham Science Publishers, 2009 ISBN 978-1-60805-207-3
^ abCotter GH, Riley WF, Beck CC, Coppock RW. Arquel (Cl- 1583). A new nonsteroidal anti-inflammatory drug for horses, in Proceedings. Am Assoc Equine Practnr 1973;19: 81–90.
^Snow DH, Baxter P, Whiting B. The pharmacokinetics of meclofenamic acid in the horse. J Vet Pharmacol Ther 1981; 4:147–156.
^ abLees P, Higgins AJ. Clinical pharmacology in therapeutic uses of non-steroidal anti-inflammatory drugs in the horse. Equine Vet J 1985;17:83–96.
^Juby, Peter F.; Hudyma, T. W.; Brown, Morton (1968). "Preparation and antiinflammatory properties of some 5-(2-anilinophenyl)tetrazoles". Journal of Medicinal Chemistry11 (1): 111–7. doi:10.1021/jm00307a025. PMID5637153.