EFFECTS OF 2-(3,4-DIMETHOXYPHENYL)ETHYLAM INE DERIVATIVE (ECABAPIDE, DQ-2511) AND ITS METABOLITES ON WATER-IMMERSION RESTRAINT STRESS-INDUCED GASTRIC-ULCERS IN RATS

Ecabapide (DQ-2511) has been demonstrated to be effective in preventin g water-immersion restraint stress ulceration of rats. In the present study, we aimed to define the active molecular features of ecabapide. Seven of 9 degraded materials identified as ecabapide metabolites were synthesized and their antiulcer activities were compared with that of the parent compound. Ecabapide was potent to prevent gastric ulcer fo rmation at the doses of 30-300 mg/kg i.p. Three metabolites (V, VIII a nd IX) were also active to inhibit ulceration induced by the stress. T he antiulcer activity of IX was similar to that of ecabapide, whereas V and VIII had less activities. After the oral administration of ecaba pide, the plasma levels of IX reached to less than 15% of that of ecab apide and also IX was largely excreted into the feces. Therefore, the potential implication of the metabolite (IX) as the active component i n the antiulcer effect of ecabapide could be excluded. Furthermore, it is also unlikely that the high polar metabolites (IV and VII) are imp licated in significant contribution for antiulcer action. In conclusio n, we have shown that ecabapide prevents water-immersion restraint str ess-induced gastric ulcers, and that this activity is probably mediate d by the action of the parent compound.