Abstract
The anti-inflammatory and analgesic properties of K-308 and K-309, new non-steroidal compounds synthesized at Tokyo Tanabe Pharmaceutical Co., were assessed by detailed analysis in comparison with known anti-inflammatory agents. Orally in rats, K-308 and K-309 showed almost the same effect as ibufenac (IF) and ibuprofen (IP) in inhibiting such acute inflammation as various phlogist-induced paw edema and increased vascular permeabilities. This effect of K-308 and K-309 was also found in adrenalectomized rats and both compounds lacked thymolytic activity. K-308 and IF revealed similar inhibitory action on ultraviolet erythema in guinea pig, but were 0.1 times as active as IP. K-309 was somewhat weaker than K-308. On such subacute inflammation as sustained paw edema induced by mustard, granulation formation by cotton pellet or granuloma pouch and adjuvant arthritis, K-308 produced a similarly significant effect to IF without impairing growth in rats. K-309, like IP, was slightly more potent than K-308. Both K-308 and K-309 produced an acute stomach ulcer in fasting rats, but the activity was lower than that of IF and IP. Utilizing the writhing and Haffner methods in mice for analgesic action, K-308 and K-309 were respectively 1 and 0.6 times as active as aminopyrine. With the Randall and Selitto's method in rats, both compounds increased pain threshold in the inflamed foot, but not in the normal foot. K-308 and K-309 exerted the same PSP retention in rabbit serum as phenylbutazone, which showed uricosuric action. Both K-308 and K-309 can therefore be considered effective for certain inflammatory conditions.
