Miyata K, Kamato T, Nishida A, Honda K
Department of Pharmacology, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Jpn J Pharmacol. 1991 Feb;55(2):211-22. doi: 10.1254/jjp.55.211.
The effect of famotidine on gastric lesions induced by the decrease in mucosal defensive resistance was investigated in rats and compared with those of cimetidine, pirenzepine and cetraxate. Famotidine (0.03, 0.1 and 0.3 mg/kg, p.o.) inhibited dose-dependently the development of gastric lesions produced by taurocholate-histamine in doses that suppressed histamine-induced acid secretion in pylorus-ligated rats. The H2-antagonist also prevented gastric mucosal lesions induced by taurocholate-serotonin, iodoacetamide, acidified aspirin and acidified ethanol. Cimetidine, pirenzepine and cetraxate showed the inhibitory effects on almost all types of the gastric lesions, but their inhibitory effects were much less potent than those of famotidine. On the other hand, famotidine inhibited the decreases of gastric mucosal blood flow induced by acidified ethanol and the mucosal contents of glycoprotein induced by water immersion restraint stress. In addition, famotidine increased the transgastric potential difference (PD) and promoted the recovery of decreased transgastric PD induced by acidified ethanol in rats. These results suggest that the preventive effect of famotidine on gastric lesions is attributable not only to suppression of acid secretion but to activation of the gastric mucosal defensive mechanisms.
研究了法莫替丁对大鼠因黏膜防御抵抗力降低所致胃损伤的影响，并与西咪替丁、哌仑西平和赛法酯进行了比较。法莫替丁（0.03、0.1和0.3毫克/千克，口服）剂量依赖性地抑制了在抑制幽门结扎大鼠组胺诱导胃酸分泌的剂量下，牛磺胆酸盐-组胺所致胃损伤的发展。这种H2拮抗剂还预防了牛磺胆酸盐-5-羟色胺、碘乙酰胺、酸化阿司匹林和酸化乙醇所致的胃黏膜损伤。西咪替丁、哌仑西平和赛法酯对几乎所有类型的胃损伤均显示出抑制作用，但其抑制作用远不如法莫替丁有效。另一方面，法莫替丁抑制了酸化乙醇所致胃黏膜血流量的减少以及水浸束缚应激所致胃黏膜糖蛋白含量的降低。此外，法莫替丁增加了大鼠胃跨膜电位差（PD），并促进了酸化乙醇所致降低的胃跨膜PD的恢复。这些结果表明，法莫替丁对胃损伤的预防作用不仅归因于胃酸分泌的抑制，还归因于胃黏膜防御机制的激活。
