ANTI-INFLAMMATORY, ANTIPYRETIC AND ANTINOCICEPTIVE PROPERTIES OF N-(2,3-XYLYL)ANTHRANILIC ACID (MEFENAMIC ACID)

¹ Departments of Pharmacology and Chemistry, Research Division, Parke, Davis & Company, Ann Arbor, Michigan

N-(2,3-xylyl)anthranilic acid (CI-473; mefenamic acid) is an anti-inflammatory agent with an acute potency 0.51 (0.37 to 0.71)_95% that of phenylbutazone as determined orally in the UV-erythema assay in guinea pigs. In the subcutaneous cotton-pellet test in rats it exhibits a significantly though shallowly dose-graded anti-granulation effect, paralleling that of phenylbutazone at a subacute (oral) potency of 0.6 (0.1 to 2.1)_95%, without adrenal dependence or significant corticoid hormonal effects. It antagonizes yeast pyresis in rats with about the same acute oral potency as phenylbutazone. In quantitative tail-pinching experiments with rats, CI-473 exhibits a grade of antinociceptive effect approximating that of aminopyrine, with a mg potency 1.4 (0.95 to 2.0)_95% times that of aminopyrine 30 minutes after intraperitoneal administration. Its dose-effect relationship is altered qualitatively in guinea pigs on intragastric administration in solution (as a salt) in the presence of food. The sodium salt is a tissue irritant in rodents, in concentrations suitable for ordinary parenteral administration, though supratherapeutic dosage rates are systemically tolerated by the intravenous route in rats. Twenty rats, half of them adrenalectomized, tolerated the finely suspended free acid by gavage at the rate of 100 mg/kg day for 7 days without incident.

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