Analgesic and anti-inflammatory activities in rats of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its intestinal damage.
alpha-(3,5-Di-t-butyl-4-hydroxybenzylidene)-gamma-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.
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D000085:Acetates / Q000037:antagonists & inhibitors; D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000188:drug therapy; D005663:Furans / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007410:Intestinal Diseases / Q000139:chemically induced; D007928:Lethal Dose 50; D008297:Male; D009288:Naproxen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D009288:Naproxen; C043236:KME 4; D015107:4-Butyrolactone; D019342:Acetic Acid; D007052:Ibuprofen; D007213:Indomethacin