Narikawa H, Oyama R, Harigaya S
Nihon Yakurigaku Zasshi. 1981 Aug;78(2):71-8.
As quaternary ammonium compounds are generally not absorbed from gastric mucosa, the direct action of these compounds on the gastric mucosa can be investigated by means of intragastric (oral) administration to pylorus ligated animals. Effects of timepidium bromide (TB), an anti-cholinergic quaternary ammonium compound, on gastric secretion of pylorus ligated rats were investigated. When TB (100 mg/Kg) was administered orally, the secretion volume of gastric juice decreased slightly, while the concentrations of free acid and pepsin in gastric juice decreased remarkably. When TB was administered intraduodenally (100 mg/kg) or subcutaneously (10 mg/kg), secretion of gastric juice and free acid was strongly inhibited, but the pepsin concentration in gastric juice was not influenced (i.d.) or slightly increased (s.c.). In the oral administration of various drugs such as atropine, hyoscine-N-butylbromide and oxethazaine (Ox), only Ox caused a decrease in pepsin concentration in gastric juice. Similar effects of TB on the pepsin concentration in the gastric juice were also observed in experiments using stomach perfused rats. TB has no effect on enzymatic activity of pepsin in in vitro experiments. From these results, it is assumed that TB inhibits acid and pepsin secretion mainly by a direct action on the gastric mucosa.
由于季铵化合物一般不会从胃黏膜吸收,因此可通过对幽门结扎动物进行胃内(口服)给药来研究这些化合物对胃黏膜的直接作用。研究了抗胆碱能季铵化合物替哌溴铵(TB)对幽门结扎大鼠胃液分泌的影响。口服TB(100mg/Kg)时,胃液分泌量略有下降,而胃液中游离酸和胃蛋白酶的浓度显著下降。十二指肠内注射(100mg/kg)或皮下注射(10mg/kg)TB时,胃液和游离酸的分泌受到强烈抑制,但胃液中胃蛋白酶浓度未受影响(十二指肠内注射)或略有升高(皮下注射)。在口服各种药物如阿托品、丁溴东莨菪碱和奥昔卡因(Ox)时,只有Ox导致胃液中胃蛋白酶浓度下降。在使用胃灌注大鼠的实验中也观察到了TB对胃液中胃蛋白酶浓度的类似作用。在体外实验中,TB对胃蛋白酶的酶活性没有影响。从这些结果推测,TB主要通过对胃黏膜的直接作用来抑制胃酸和胃蛋白酶的分泌。