Nielsen S T
J Pharmacol Exp Ther. 1987 Aug;242(2):607-13.
Wy-45,727, structurally similar to ranitidine, was characterized in various models to define its gastric acid antisecretory potency and mechanism of action. In vitro it antagonized the histamine-induced 1) positive chronotropism in isolated guinea pig right atria (pA2 = 8.23, Schild coefficient +/- S.E.M. = 1.09 +/- 0.01), and 2) [14C]aminopyrine uptake in rat isolated gastric mucosal cells. It inhibited acid secretion in dogs (p.o.) prepared with innervated gastric pouches (ED50 = 0.2 mg/kg) and in the pylorus-ligated rat (ED50 = 0.43 mg/kg). ED50 values for ranitidine were 0.9 mg/kg (dog) and 9.97 mg/kg (rat). After an 18-hr pretreatment period with doses up to 300 mg/kg p.o., inhibition of acid secretion in the rat barely exceeded 50%, indicating that the duration of action of Wy-45,727 was not excessive. Wy-45,727 appears to be a selective histamine H2 receptor antagonist.
Wy-45727在结构上与雷尼替丁相似，在多种模型中对其进行了特性研究，以确定其胃酸分泌抑制效力和作用机制。在体外，它拮抗组胺诱导的：1）豚鼠离体右心房的正性变时作用（pA2 = 8.23，希尔德系数±标准误 = 1.09 ± 0.01），以及2）大鼠离体胃黏膜细胞对[14C]氨基比林的摄取。它抑制用带神经支配胃小囊制备的犬（口服）的胃酸分泌（ED50 = 0.2 mg/kg）和幽门结扎大鼠的胃酸分泌（ED50 = 0.43 mg/kg）。雷尼替丁的ED50值分别为0.9 mg/kg（犬）和9.97 mg/kg（大鼠）。口服高达300 mg/kg剂量进行18小时预处理后，大鼠胃酸分泌的抑制率仅略超过50%，这表明Wy-45727的作用持续时间并不过长。Wy-45727似乎是一种选择性组胺H2受体拮抗剂。
