Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent

Abstract

Abstract Nabumetone is a compound of novel structure which displays acute anti-inflammatory activity in the carrageenan-induced oedema model in rats and the ultraviolet-induced erythema model in guinea-pigs. Its activity in these tests is greater than that of aspirin but less than that of naproxen and indomethacin. In the cotton pellet-induced granuloma model in the rat, the compound is active and produces no signs of toxicity at doses much greater than the lowest effective dose, unlike aspirin, naproxen or indomethacin. Nabumetone is also active in the adjuvant-induced arthritis test in rats. In contrast to aspirin, indomethacin and naproxen, the compound is well tolerated by the stomach of fasted rats at doses in excess of those with anti-inflammatory activity. These findings could be linked to the relatively poor ability of nabumetone to inhibit the synthesis of prostaglandins in vitro and to its non-acidic structure. The compound has greater mild analgesic activity than paracetamol, is equi-active with phenylbutazone, but less active than aspirin, naproxen and indomethacin. Nabumetone also has antipyretic activity in the rabbit. No interactions with the hypothalamic-pituitary-adrenal axis have been found.