Effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on the established adjuvant arthritis in rats.

The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on established adjuvant arthritis in rats was compared to that of indomethacin. When administered orally daily from days 14 to 27 starting on day 14 after the adjuvant (day 0), KME-4 (2 to 10 mg/kg) produced a dose-related reduction of the swelling of both injected and uninjected hindpaws, and it retarded body weight loss. The initiation of paw swelling after the cessation of therapy was not observed at either 5 mg/kg or 10 mg/kg of KME-4. On day 42 (15 days after discontinuation of dosing), KME-4 caused the recovery of organ weight, erythrocyte sedimentation rate (ESR) and serum albumin/globulin (A/G) ratio towards normal levels, and it also decreased radiographic bone damage scores in a dose-dependent manner. The results indicate that KME-4 produces the improvement of systemic symptoms in the established adjuvant arthritis. The results obtained with indomethacin were similar to those with KME-4. However, the degree of the efficacy of indomethacin (2 mg/kg) was lower than that of KME-4 (10 mg/kg) as judged by the measured parameters (ESR, serum A/G ratio and bone damage).