Abstract
A new derivative of aspirin, N-3'a-propyphenazonyl-2-acetoxybenzamide (aspirin-isopropylantipyrine, AIA) was synthesized, and its gastric ulcerogenic and biological activities were investigated together with those of related compounds. AIA (100, 200 mg/kg, p. o., i. p.) showed much less gastric ulcerogenic activity than aspirin in pylorus-ligated rats. The effect of AIA on the stomach was also weaker than those of salicylate-IA (SIA), salicyloyl leucine (SL), salicyloyl methionine (SM) and IA. AIA (200 mg/kg, p. o.) did not injure the stomachs of adjuvant arthritis rats given the drug daily for 21 days, unlike aspirin. However, AIA (100 mg/kg, i. p.) did not improve the gastric ulcerations induced by pylorus ligation, histamine, acetic acid and stress in rats. AIA showed analgetic activity (100, 200 mg/kg, s. c.) in the acetic acid method and the D'Amour-Smith method in mice, antipyretic activity (100 mg/kg, s. c.) in rats treated with E. coli, inhibitory activity (100 mg/kg, s. c.) on carrageenin edema formation in rats and inhibitory activity (200 mg/kg/day×21, p. o.) on adjuvant arthritis in rats. SL (100 mg/kg, s.c.) showed analgetic and antipyretic activities, while SIA (100 mg/kg, s. c.) showed only analgetic activity, and SM (100 mg/kg, s. c.) did not show any activity. These compounds were inactive on carrageenin edema formation, unlike AIA and aspirin. AIA (10-4g/ml) inhibited the contraction of isolated ileum preparations stimulated by histamine, anetyl-choline and barium chloride, but had no effect on anaphylactic shock of the ileum sensitized by egg albumin, AIA had no effect on increased vascular permeability in mice, rabbit blood pressure and the beating of perfused frog heart. The acute toxicity of AIA in mice was much less than that of aspirin, as shown by the LD50 values which were more than 5g/kg p.o., s.c. and 3.68 g/kg i.p. for AIA.
