6-[1S-(3S,4-Dihydro-8- hydroxy-1H-2-benzo-
pyran-1-one-3-yl)- methylbutylamino]-4S,5S-dihydroxy-6-oxo-3S-ammoniohexanoate (AI-77B)-gamma-lactone-N-ethyl derivative (AI-77-C2) is a new antiinflammatory
drug with antiulcer activity. In the first part of the present study the ulcerogenicity of this
drug was assessed. Acidic antiinflammatory drugs--
indomethacin and
diclofenac--and basic antiinflammatory drugs--
tiaramide and
mepirizole--were used for comparison. Although AI-77-C2 was barely ulcerogenic at 7 h after dosing, some lesions developed in both stomach and intestine at 24 h. Repeated administrations over 5 days appeared to increase its ulcerogenicity and general toxicity. Marked
gastric ulcers were induced by
indomethacin and
diclofenac, and severe intestinal
ulcers were also produced at 24 h and by their repeated administration.
Tiaramide did not induce marked
ulcers in any case. Although the ulcerogenicity of
mepirizole was weak at 7 h, severe
duodenal ulcers developed at 24 h and after the repeated administration. From the results given above, it was concluded that the ulcerogenicity of AI-77-C2 was relatively low. In the next study, the antiulcer activity of AI-77-C2 was examined in several experimental
ulcer models. AI-77-C2 showed a marked inhibition of all the models presently employed, i.e., the
indomethacin-induced
gastric ulcer, the pylorus
ligation ulcer, the water immersion stress
ulcer, and the
acetylsalicylic acid-induced
ulcer in rats. It was observed that AI-77-C2 suppressed the gastric secretion and movement. It is therefore concluded that the antiinflammatory
drug AI-77-C2 has low ulcerogenicity and potent antiulcer activity.(ABSTRACT TRUNCATED AT 250 WORDS)