Pharmacological studies of 2-(5H-(1)benzopyrano(2,3-b)pyridin-7-yl)propionic acid (Y-8004). (I) Anti-inflammatory, analgesic and antipyretic actions

Abstract

A newly synthesized anti-inflammatory agent, Y-8004 demonstrated a greater inhibition than did indomethacin (IM). on inflammatory response such as ultraviolet erythema in guinea pigs, carrageenin edema, evans blue and carrageenin-induced pleuritis and acetic acid-induced peritonitis in rats. On the other hand, the inhibition of Y-8004 was to the same extent as IM regarding granuloma formation around cotton pellet and the development of adjuvant arthritis in rats, however, Y-8004 was only half as effective as IM regarding exudation in granuloma pouch. In addition, the agent was effective in alleviating established adjuvant arthritis, the anti-inflammatory activity was not mediated by stimulation of the adrenals, and glucocorticoid-like activity could not be demonstrated. Furthermore, analgesic and antipyretic activities were to the degree as seen with IM, and the analgesic property of Y-8004 was considered to be peripheral as is the case with IM. The ulcerogenic activity of Y-8004 was observed to be mainly in the jejunum and ileum of the rat, but compared to IM, there were considerable differences between the ulcerogenic and the effective doses. As Y-8004 has a wider therapeutic margin than IM, this non-steroidal anti-inflammatory agent should be quite applicable for clinical purposes.