Yasuzo Hiramatsu

Analgesic and anti-inflammatory activities in rats of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its intestinal damage

α‐(3,5‐Di‐t‐butyl‐4‐hydroxybenzylidene)‐γ‐butyrolactone (KME‐4), an anti‐inflammatory drug, possesses analgesic activity in rat models. In the acetic acid‐induced writhing test, the oral ED50 values for KME‐4, indomethacin, naproxen and ibuprofen were 5.2, 3.8,7.0 and 18.6 mg kg−1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid‐induced vascular permeability in rats. KME‐4 also had analgesic activity in the tests of Randall‐Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME‐4 (10 mg kg−1 day−1 orally) has a preventive effect against adjuvant‐induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg−1 day−1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME‐4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen.