ro-22-6923 and Stomach-Ulcer

Effects of OKY-046, a thromboxane synthetase inhibitor; BM 13.177, a thromboxane A2-receptor antagonist and FPL 55712, a leukotriene antagonist have been studied on gastric lesions induced by necrotizing agents (80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 100 mM sodium taurocholate), aspirin, indomethacin, reserpine and hypothermic restraint stress in rats. Ro 22-6923, a synthetic trimethyl prostanoid has been used for comparison. OKY-046, FPL 55712 and Ro 22-6923 produced dose dependent inhibition of gastric lesions induced by necrotizing agents and reduced the severity of aspirin, indomethacin, reserpine and hypothermic restraint stress induced lesions. BM 13.177 was not found effective against any of the models used in this study. These observations indicate towards the role of thromboxane A2 and leukotriene C4 in the genesis of gastric lesions induced by different methods. FPL 55712 required considerably lower doses than those of OKY-046 to display its protective effects in these models. Further studies on the levels of thromboxane A2 and leukotriene C4 in the gastric mucosa, are suggested to substantiate these observations.

Topics: Animals; Anti-Ulcer Agents; Chromones; Female; Fibrinolytic Agents; Male; Methacrylates; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; SRS-A; Stomach Ulcer; Sulfonamides; Thromboxane A2

Ro 22-6923, a synthetic trimethyl prostanoid, has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAIDs), reserpine, dimaprit, cysteamine and the cytodestructing agents--80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl, aspirin 30 mg in 0.35 M HCl and 100 mM sodium taurocholate in 0.2 M HCl. The results of this study demonstrate that Ro 22-6923 has both prophylactic and curative effects on various experimental models. It produces a dose dependent inhibition of the gastric mucosal damage induced by pyloric ligation, hypothermic restraint stress, NSAIDs, reserpine, dimaprit and cytodestructing agents and that of duodenal ulcers induced by cysteamine. It also produces a dose dependent healing of the acetic acid induced chronic gastric ulcers. These observations suggest that Ro 22-6923 exerts its anti-ulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities and that it may be a useful therapeutic agent for the treatment of peptic ulcer disease in humans.

Topics: Animals; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Male; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer