PT  - JOURNAL ARTICLE
AU  - Satoh, H
AU  - Inatomi, N
AU  - Nagaya, H
AU  - Inada, I
AU  - Nohara, A
AU  - Nakamura, N
AU  - Maki, Y
TI  - Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats.
DP  - 1989 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 806--815
VI  - 248
IP  - 2
4099  - http://jpet.aspetjournals.org/content/248/2/806.short
4100  - http://jpet.aspetjournals.org/content/248/2/806.full
SO  - J Pharmacol Exp Ther1989 Feb 01; 248
AB  - The antisecretory and antiulcer activities of 2[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazole (AG-1749) were investigated in dogs and rats. AG-1749 inhibited both the (H+ + K+)-adenosine triphosphatase activity in canine gastric microsomes and dibutyryl cyclic AMP-stimulated acid formation in isolated canine parietal cells and suppressed the acid secretion stimulated by histamine, pentagastrin, bethanechol or a peptone meal in Heidenhain pouch dogs; the ID50 values were between 0.2 and 0.7 mg/kg p.o. AG-1749 inhibited both the histamine-stimulated and the basal acid secretion in pylorusligated rats and prevented water immersion stress or aspirin-induced gastric lesions and mepirizole or cysteamine-induced duodenal ulcers in rats; the ID50 values were between 0.3 to 3.6 mg/kg p.o. or i.d. Furthermore, AG-1749 prevented gastric lesions induced by absolute ethanol or acidified aspirin, and accelerated the healing of acetic acid-induced gastric or duodenal ulcers in rats. The inhibitory potency of AG-1749 in dogs was much the same as that of omeprazole and about half that of ranitidine. However, it was about 2 to 10 times more potent than omeprazole and 4 to 34 times more potent than ranitidine in rats. These results suggest that AG-1749 exerts prominent antiulcer activities mainly by suppressing acid secretion via an inhibition of a proton pump in gastric parietal cells and partly by protecting the gastrointestinal mucosa against various ulcerative stimuli.