Abstract
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.
MeSH Terms
Adult
Clinical Trials as Topic
Drug Therapy, Combination
Duodenal Ulcer/metabolism,physiopathology
Female
Food
Gastric Juice/metabolism
Gastrins/blood
Gastrointestinal Motility/drug effects
Histamine
Humans
Imidazoles/pharmacology
Male
Middle Aged
Placebos
Quaternary Ammonium Compounds/pharmacology
Receptors, Drug
Stomach/drug effects,physiopathology
Sulfides
Thiourea/analogs & derivatives,pharmacology
Chemicals
Gastrins
Imidazoles
Placebos
Quaternary Ammonium Compounds
Receptors, Drug
Sulfides
Histamine
Thiourea
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Richardson C T
Bailey B A
Walsh J H
Fordtran J S
References (12)
12 references, click to expand
-
MEASUREMENT AND NOMENCLATURE OF GASTRIC ACID.
Gastroenterology. 1963 Jul;45:118-21
PMID: 14046305
-
Optimal effective dose of anticholinergic drug in peptic ulcer therapy.
AMA Arch Intern Med. 1956 Apr;97(4):442-52
PMID: 13301078
-
THE DETERMINATION OF GASTRIC ACIDITY BY THE GLASS ELECTRODE.
Gastroenterology. 1965 Aug;49:178-88
PMID: 14323728
-
THE EFFECT OF POLDINE, GLYCOPYRROLATE AND 1-HYOSCYAMINE ON GASTRIC SECRETION OF ACID IN MAN.
Acta Med Scand. 1965 Feb;177:169-74
PMID: 14279498
-
THE EFFECT OF GLYCOPYRROLATE ON NOCTURNAL GASTRIC SECRETION IN PEPTIC ULCER PATIENTS.
Am J Med Sci. 1963 Sep;246:325-8
PMID: 14063751
-
New clinical method for measuring the rate of gastric emptying: the double sampling test meal.
Gut. 1968 Apr;9(2):237-42
PMID: 4871724
-
Inhibition of nocturnal acid secretion in duodenal ulcer by one oral dose of metiamide.
Lancet. 1974 Apr 20;1(7860):693-4
PMID: 4132419
-
Definition and antagonism of histamine H 2 -receptors.
Nature. 1972 Apr 21;236(5347):385-90
PMID: 4401751
-
Inhibition of acid secretion in dog by metiamide, a histamine antagonist acting on H2 receptors.
Gastroenterology. 1974 Apr;66(4):517-21
PMID: 4150710
-
Receptors mediating some actions of histamine.
Br J Pharmacol Chemother. 1966 Aug;27(2):427-39
PMID: 4381779
-
Gastric acid secretion rate and buffer content of the stomach after eating. Results in normal subjects and in patients with duodenal ulcer.
J Clin Invest. 1973 Mar;52(3):645-57
PMID: 4685087
-
Effect of isopropamide iodide on basal gastric secretion in the human.
Gastroenterology. 1957 Nov;33(5):730-6
PMID: 13480414