Effect of SR 58611A, a beta-3 receptor agonist, against experimental gastro-duodenal ulcers.

The present study was designed to study the effect of SR 58611A, a selective beta 3-adrenoceptor agonist against gastric ulcers: pylorus ligation, water immersion plus restraint stress (WIRS), ethanol, aspirin-induced and on cysteamine-induced duodenal ulcers, in rats. SR 58611A (10 mg/kg, p.o.) was found to be effective in attenuating gastric ulceration and the results were comparable with those from standard cimetidine-treated group. Apart from reducing ulcer index, SR 58611A significantly decreased total acidity and thereby exhibited antisecretory activity in pylorus ligation model. SR 58611A showed significant reduction in ulcer index alongwith significant rise in the gastric wall mucus content in WIRS model. Further it showed significant cytoprotective activity against ethanol insult, that was evident from significant reduction in ulcer index. It showed significant reduction in gastric ulceration in aspirin-treated rats. The drug was found to be ineffective in inhibiting the cysteamine-induced duodenal ulcers as evident from the ulcer index and total lesion area parameters. It is concluded that SR 586111A possesses significant gastroprotective activity. This activity could be attributed to the inhibition of gastric acidity, increase in gastric wall mucus content and the reversal of gastric microvascular injury resulting into protection of the vascular integrity.