Richardson C T, Bailey B A, Walsh J H, Fordtran J S
J Clin Invest. 1975 Mar;55(3):536-42. doi: 10.1172/JCI107960.
The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying.
本系列实验的目的是测量并比较一种抗胆碱能药物(异丙胺酰)和组胺H2受体拮抗剂(甲硫米特)对食物刺激胃酸分泌的影响。十二指肠溃疡患者通过进食牛排餐受到刺激,胃酸分泌通过体内胃内滴定法进行测量。临床上服用不会产生无法耐受副作用的最大剂量异丙胺酰(最大耐受剂量)可使食物刺激的胃酸分泌减少35%。相比之下,400毫克剂量的甲硫米特未产生副作用,且几乎完全消除了食物刺激的胃酸分泌。剂量反应曲线显示,抑制食物刺激的胃酸分泌50%需要50毫克剂量的甲硫米特。进一步研究表明,甲硫米特和异丙胺酰在抑制食物刺激的胃酸分泌方面具有相加作用,且甲硫米特对血清胃泌素浓度或胃排空无影响。