[Effects of 2-(3,4-dimethoxyphenyl)ethylamine 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 preventing 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 formation at the doses of 30-300 mg/kg i.p. Three metabolites (V, VIII and IX) were also active to inhibit ulceration induced by the stress. The antiulcer activity of IX was similar to that of ecabapide, whereas V and VIII had less activities. After the oral administration of ecabapide, the plasma levels of IX reached to less than 15% of that of ecabapide and also IX was largely excreted into the feces. Therefore, the potential implication of the metabolite (IX) as the active component in the antiulcer effect of ecabapide could be excluded. Furthermore, it is also unlikely that the high polar metabolites (IV and VII) are implicated in significant contribution for antiulcer action. In conclusion, we have shown that ecabapide prevents water-immersion restraint stress-induced gastric ulcers, and that this activity is probably mediated by the action of the parent compound.
Hosokami
T
T
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tabuchi
Y
Y
Furuhama
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007101:Immersion; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications*; D013329:Structure-Activity Relationship; D014867:Water
D000897:Anti-Ulcer Agents; D001549:Benzamides; D014867:Water; C058308:ecabapide