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.