Konturek P C, Brzozowski T, Konturek S I, Márquez M, Torres J, Ortiz J A
Institute of Physiology, Jagiellonian University School of Medicine, Krakow, Poland.
Arzneimittelforschung. 1997 Apr;47(4A):578-89.
Gastric mucosa is exposed to various aggressive factors such as stress, ulcerogenic drugs including acetyl-salicylic acid(ASA)-like agents, ethanol, bacteria, particularly Helicobacter pylori (Hp), and various endogenous irritants such as acid-pepsin secretion and bile salts. The maintenance of the mucosal barrier depends upon the activation of the pre-epithelial (mucus-alkali secretion), epithelial (surface-active phospholipids and rapid mucosal restitution) and post-epithelial (mucosal microcirculation, sensory nerves and mast cells) components of mucosal defense. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamid e, CAS 100981-43-9, FI-3542) is the first of a new generation of H2-receptor antagonists with both antisecretory and cytoprotective activities. Its inhibitory action is similar to that of ranitidine and approximately tenfold greater than cimetidine, and is accompanied by a small and transient increase in plasma gastrin levels. In contrast to ranitidine and other H2-receptor antagonists, ebrotidine exerts a unique cytoprotection against injury by various ulcerogens such as ethanol, ammonia, lipopolysaccharides (LPS), stress and ASA or acidified taurocholate. The mechanism of this protection by ebrotidine is not clear, but it has been shown to stimulate mucus secretion, to increase the quality of adherent mucus gel and to increase gastric mucosal blood flow (GBF), possibly due to enhanced mucosal formation of prostaglandin E2 (PGE2) and nitric oxide (NO). The cytoprotective effects of ebrotidine were observed in rats and confirmed also in humans with gastric lesions induced by ethanol or ASA. Ebrotidine also exerts anti-Helicobacter pylori (Hp) effects by interfering with surface receptors of epithelial cells and inhibiting urease, protease and lipase activity, and by counteracting the noxious effects of Hp-related substances such as ammonia and lipopoly-saccharides (LPS).
胃黏膜会接触到各种侵袭性因素，如应激、包括乙酰水杨酸（ASA）类药物在内的致溃疡药物、乙醇、细菌，尤其是幽门螺杆菌（Hp），以及各种内源性刺激物，如胃酸-胃蛋白酶分泌和胆汁盐。黏膜屏障的维持取决于黏膜防御的上皮前（黏液-碱分泌）、上皮（表面活性磷脂和快速的黏膜修复）和上皮后（黏膜微循环、感觉神经和肥大细胞）成分的激活。依罗替丁（N-[(E)-[[2-[[[2-[(二氨基亚甲基)氨基]-4-噻唑基]甲基]硫代]乙基]氨基]亚甲基]-4-溴苯磺酰胺，CAS 100981-43-9，FI-3542）是新一代具有抗分泌和细胞保护活性的H2受体拮抗剂中的首个药物。其抑制作用与雷尼替丁相似，比西咪替丁大约强十倍，且会伴随血浆胃泌素水平的小幅短暂升高。与雷尼替丁和其他H2受体拮抗剂不同，依罗替丁对乙醇、氨、脂多糖（LPS）、应激和ASA或酸化牛磺胆酸盐等各种致溃疡物质所致的损伤具有独特的细胞保护作用。依罗替丁这种保护作用的机制尚不清楚，但已表明它能刺激黏液分泌，提高附着黏液凝胶的质量，并增加胃黏膜血流量（GBF），这可能是由于黏膜前列腺素E2（PGE2）和一氧化氮（NO）的生成增强。依罗替丁的细胞保护作用在大鼠中得到观察，并在乙醇或ASA诱导胃损伤的人类中也得到证实。依罗替丁还通过干扰上皮细胞的表面受体、抑制脲酶、蛋白酶和脂肪酶活性，以及抵消Hp相关物质如氨和脂多糖（LPS）的有害作用，发挥抗幽门螺杆菌（Hp）的作用。
