Gastroprotective effect of beta3 adrenoreceptor agonists ZD 7114 and CGP 12177A in rats.

The effects of beta(3) adrenergic receptor agonists, (S)-4-[2-hydroxy-3-phenoxy-propylamino-ethoxy]-N-(2-methoxyethyl)-phenoxyacetamide (ZD 7114) and (+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP 12177A), were studied on aspirin plus pylorus ligation-induced gastric ulcers, gastric mucosal blood flow and gastric motility in rats. Pretreatment with ZD 7114 (3 mg kg(-1), p.o.) and CGP 12177A (3.5 mg kg(-1), p.o.) resulted in significant reduction in the incidences of gastric ulceration in aspirin plus pylorus ligated rats and results were comparable with the cimetidine treated group. Ulcer index was significantly reduced by ZD 7114 (0.71+/-0.05, P<0.05) and CGP 12177A (1.15+/-0.27, P<0.05) when compared with the control group (4.47+/-0.38). Further, significant increase in total carbohydrates to protein content ratio (mucin activity) was also observed. However, they did not alter the acid secretory parameters such as total acidity, total acid output and pepsin activity. Effects of ZD 7114 and CGP 12177A on gastric mucosal blood flow were studied using neutral red clearance method. Both the treatments showed significant increase in gastric mucosal blood flow (GV/Bt) as compared to control group. Effect on gastric motility was evaluated by estimation of phenol red concentration in rat stomach. Significantly higher concentrations of phenol red in the stomach were observed in ZD 7114 and CGP 12177A treated rats. Both ZD 7114 and CGP 12177A showed significant gastroprotective effect in the present study. The mechanism of this effect may be attributed to enhancement of gastric mucosal blood flow, reduction in gastric motility and strengthening of gastric mucosal barrier.