Ichikawa T, Ishihara K, Shibata M, Yamaura T, Saigenji K, Hotta K
Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.
Eur J Pharmacol. 1996 Feb 15;297(1-2):87-92. doi: 10.1016/0014-2999(95)00731-8.
Certain chemical properties, which may determine the stimulatory actions of the new histamine H2 receptor antagonist, FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(Z)- 2-butenyl)acetamide), on mucin biosynthesis, were identified by considering the derivation of this drug using an organ culture system of the rat stomach. [3H]Glucosamine and [35S]sulfate incorporation was stimulated in the corpus region by FRG-8813 and its structural analog, compound A (N-[4-[[4- (piperidinylmethyl)pyridyl]-2-oxy]-(Z)-2-butenyl]phthalimide). The chronotropic response to histamine in the guinea pig right atria was suppressed by FRG-8813 in a concentration-dependent fashion. In contrast, compound A did not suppress the histamine-induced response. Ranitidine at 10(-4) M did not suppress the FRG-8813-induced increase in [3H]glucosamine incorporation into mucin. These results suggest that the pyridine derivative and amide structure are chemically important in FRG-8813 as a stimulant on mucus metabolism. Also, this effect is not directly due to histamine H2 receptor antagonism.
通过使用大鼠胃的器官培养系统研究这种药物的衍生物，确定了某些化学性质，这些性质可能决定新型组胺H2受体拮抗剂FRG-8813（2-(糠基亚磺酰基)-N-(4-[4-(哌啶甲基)-2-吡啶基]氧基-(Z)-2-丁烯基)乙酰胺）对粘蛋白生物合成的刺激作用。FRG-8813及其结构类似物化合物A（N-[4-[[4-(哌啶基甲基)吡啶基]-2-氧基]-(Z)-2-丁烯基]邻苯二甲酰亚胺）刺激了胃体区域的[3H]葡萄糖胺和[35S]硫酸盐掺入。FRG-8813以浓度依赖性方式抑制豚鼠右心房对组胺的变时反应。相比之下，化合物A没有抑制组胺诱导的反应。10(-4)M的雷尼替丁没有抑制FRG-8813诱导的[3H]葡萄糖胺掺入粘蛋白的增加。这些结果表明，吡啶衍生物和酰胺结构在FRG-8813作为粘液代谢刺激剂方面具有重要的化学意义。此外，这种作用并非直接由于组胺H2受体拮抗作用。
