Ulcerogenic and antiulcerogenic effects of a new antiinflammatory drug, the gamma-lactone-N-ethyl derivative of 6-[1S-(3S,4-dihydro-8-hydroxy-1H-2-benzo- pyran-1-one-3-yl)-3-methylbutylamino]-4S,5S-dihydroxy-6-oxo-3S- ammoniohexanoate, on gastrointestinal tract in rats.

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)