Differences in the antisecretory actions of the proton pump inhibitor AG-1749 (lansoprazole) and the histamine H2-receptor antagonist famotidine in rats and dogs.
Antisecretory effects of a substituted benzimidazole, (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazole (AG-1749) were compared with those of a histamine H2-receptor antagonist, famotidine. AG-1749 inhibited acid formation regardless of the stimulant in isolated canine parietal cells, while famotidine inhibited the histamine-stimulated acid formation selectively. In pylorus-ligated rats, AG-1749 suppressed basal acid secretion, histamine-, bethanechol-, pentagastrin-, 2-deoxy-D-glucose- and stress (restraint and water-immersion)-induced acid secretion; ID50 values were 1.0-6.0 mg/kg. On the other hand, famotidine only partially inhibited the acid secretion induced by 2-deoxy-D-glucose or stress, although it suppressed the acid secretion stimulated by other secretagogues several times more potently than AG-1749. The antisecretory effect of AG-1749 lasted longer than that of famotidine, especially in the case of bethanechol-stimulated acid secretion. In Heidenhain pouch dogs, both AG-1749 and famotidine potently inhibited histamine-, bethanechol-, pentagastrin- and peptone meal-stimulated acid secretion, but the inhibitory effect of famotidine was short-lived in the case of bethanechol- and pentagastrin-stimulated acid secretion. These results suggest that AG-1749 persistently inhibits acid secretion induced by both peripheral and central stimuli and suggest that the antisecretory effect of famotidine depends on the nature of the stimuli.
Nagaya
H
H
Biology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Inatomi
N
N
Satoh
H
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001626:Bethanechol Compounds / Q000494:pharmacology; D004285:Dogs; D015738:Famotidine / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D010461:Peptones / Q000494:pharmacology; D011708:Pylorus / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001626:Bethanechol Compounds; D010461:Peptones; D064747:Lansoprazole; D015738:Famotidine; D006632:Histamine; D010418:Pentagastrin; D009853:Omeprazole