Orsetti M, Sorba G
Institute of Pharmacology and Pharmacognosy, Pharmacy School, Torino, Italy.
J Pharm Pharmacol. 1988 Jan;40(1):31-4. doi: 10.1111/j.2042-7158.1988.tb05145.x.
New compounds structurally related to cimetidine, ranitidine and lamtidine have been prepared and tested for their histamine H2-receptor blocking activity on guinea-pig atria, rat perfused stomach and frog isolated gastric mucosa. These derivatives contain as a polar group, a diaminofurazan moiety, a 3-amino-4-methylfurazan or a 3-amino-4-phenylfurazan moiety. Ranitidine and lamtidine analogues display strong H2-antagonist activity in-vitro (KB on atria 0.037 microM and 0.0039 microM, respectively) and in-vivo on the lumen-perfused stomach of the anaesthetized rat (ID50 0.13 mumol kg-1 and 0.023 mumol kg-1 i.v., respectively). However, lamtidine analogues are ineffective in blocking the histamine-induced increase of H+ output in the frog isolated gastric mucosa. On the basis of the anomalous results in the frog, it is concluded that caution must be exercised in extrapolating information from amphibian to mammalian tissues with regard to the structure and the function of histamine receptors.
已制备出与西咪替丁、雷尼替丁和兰替丁结构相关的新化合物，并在豚鼠心房、大鼠灌流胃和青蛙离体胃黏膜上测试了它们对组胺H2受体的阻断活性。这些衍生物含有一个极性基团，即二氨基呋咱部分、3-氨基-4-甲基呋咱或3-氨基-4-苯基呋咱部分。雷尼替丁和兰替丁类似物在体外显示出较强的H2拮抗剂活性（在心房上的KB分别为0.037微摩尔和0.0039微摩尔），在体内对麻醉大鼠的腔灌流胃也有活性（静脉注射的ID50分别为0.13微摩尔/千克和0.023微摩尔/千克）。然而，兰替丁类似物在阻断青蛙离体胃黏膜中组胺诱导的H+分泌增加方面无效。基于青蛙实验的异常结果，得出结论：在从两栖动物组织向哺乳动物组织外推组胺受体的结构和功能信息时必须谨慎。
