Browning J G, Heathcote B V
Arch Int Pharmacodyn Ther. 1983 Jun;263(2):288-96.
The effects of pirenzepine, a muscarinic antagonist, and cimetidine, a histamine H2-receptor antagonist, on 2-deoxy-D-glucose-stimulated gastric secretion were investigated in the gastric-fistula cat. Both drugs inhibited gastric acid secretion in a dose-related manner; the oral ED50 of pirenzepine was 0.37 (0.22-0.59) mg/kg and cimetidine was 4.6 (3.3-5.8) mg/kg. The two drugs affected pepsin secretion in characteristically different ways. The inhibition of pepsin secretion by cimetidine was small and inconsistent when compared with the effect on acid. Throughout the dose-range cimetidine tended to reduce volume more than pepsin secretion. The resulting rise in concentration of pepsin suggested that cimetidine had an indirect effect on pepsin secretion. In contrast, pirenzepine exerted a direct effect on both acid and pepsin. Hence at doses producing a 50% inhibition of acid secretion pirenzepine and cimetidine reduced pepsin secretion by 78% and 25% respectively. These observations were consistent with the concept that muscarinic receptors and not histamine H2-receptors are involved in the regulation of pepsin secretion.
在胃瘘猫身上研究了毒蕈碱拮抗剂哌仑西平和组胺H2受体拮抗剂西咪替丁对2-脱氧-D-葡萄糖刺激的胃分泌的影响。两种药物均以剂量相关的方式抑制胃酸分泌；哌仑西平的口服半数有效剂量（ED50）为0.37（0.22 - 0.59）mg/kg，西咪替丁为4.6（3.3 - 5.8）mg/kg。两种药物对胃蛋白酶分泌的影响方式明显不同。与对酸的作用相比，西咪替丁对胃蛋白酶分泌的抑制作用较小且不一致。在整个剂量范围内，西咪替丁倾向于更多地减少胃液分泌量而非胃蛋白酶分泌量。胃蛋白酶浓度的相应升高表明西咪替丁对胃蛋白酶分泌有间接作用。相比之下，哌仑西平对酸和胃蛋白酶均有直接作用。因此，在产生50%胃酸分泌抑制作用的剂量下，哌仑西平和西咪替丁分别使胃蛋白酶分泌减少78%和25%。这些观察结果与毒蕈碱受体而非组胺H2受体参与胃蛋白酶分泌调节的概念一致。
