DIFFERENCES IN THE ANTISECRETORY ACTIONS OF THE PROTON PUMP INHIBITOR AG-1749 (LANSOPRAZOLE) AND THE HISTAMINE-H2-RECEPTOR ANTAGONIST FAMOTIDINE IN RATS AND DOGS

被引:18
作者
NAGAYA, H
INATOMI, N
SATOH, H
机构
[1] Biology Research Laboratories, Takeda Chemical Industries, Ltd., Yodogawa-ku, Osaka 532, 2-17-85, Juso-honmachi
关键词
D O I
10.1254/jjp.55.425
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Antisecretory effects of a substituted benzimidazole, (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-H-1-benzimidazole (AG-1749) were compared with those of a histamine H-2-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.
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页码:425 / 436
页数:12
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