DIFFERENCES IN THE ANTISECRETORY ACTIONS OF THE PROTON PUMP INHIBITOR AG-1749 (LANSOPRAZOLE) AND THE HISTAMINE-H2-RECEPTOR ANTAGONIST FAMOTIDINE IN RATS AND DOGS
DIFFERENCES IN THE ANTISECRETORY ACTIONS OF THE PROTON PUMP INHIBITOR AG-1749 (LANSOPRAZOLE) AND THE HISTAMINE-H2-RECEPTOR ANTAGONIST FAMOTIDINE IN RATS AND DOGS
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DOI：
10.1254/jjp.55.425
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发表时间：
1991-04-01
期刊：
影响因子：
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通讯作者：
SATOH, H
中科院分区：
文献类型：
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作者：
NAGAYA, H;INATOMI, N;SATOH, H
本文比较了取代苯并咪唑（+/-）-2-[3-甲基-4-（2，2，2-三氟乙氧基）-2-吡啶基]甲基]亚磺酰基]-H-1-苯并咪唑（AG-1749）与组胺H-2受体拮抗剂法莫替丁的抗分泌作用。 AG-1749抑制酸的形成，无论在离体犬壁细胞的刺激，而法莫替丁抑制组胺刺激的酸的形成选择性。 在幽门结扎大鼠中，AG-1749抑制基础酸分泌、组胺、氨甲酰胆碱、五肽胃泌素、2-脱氧-D-葡萄糖和应激（束缚和水浸）诱导的酸分泌; ID 50值为1.0-6.0 mg/kg。 另一方面，法莫替丁仅部分抑制由2-脱氧-D-葡萄糖或应激诱导的酸分泌，尽管它抑制由其他促分泌素刺激的酸分泌的效力比AG-1749强几倍。 AG-1749的抗分泌作用持续时间长于法莫替丁，尤其是在氨甲酰胆碱刺激的酸分泌的情况下。 在Heidenhain邮袋犬中，AG-1749和法莫替丁均有效抑制组胺、氨甲酰胆碱、五肽胃泌素和蛋白胨餐刺激的酸分泌，但法莫替丁对氨甲酰胆碱和五肽胃泌素刺激的酸分泌的抑制作用是短暂的。 这些结果表明，AG-1749持续抑制由外周和中枢刺激诱导的酸分泌，并表明法莫替丁的抗分泌作用取决于刺激的性质。
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.