Dose-response curve analysis of gastric secretory responses in the dog and man to impromidine: a new histamine-H2-receptor agonist

RL McIsaac, BJ Johnston and MC Flannery

The new histamine-H2-receptor agonist, impromidine, was assessed for its effect on gastric acid secretion using a dose-response format. Maximal acid output and ED50 were calculated for infusions of impromidine in the Heidenhain pouch dog (0.05-1.6 x 10(-8) mol/kg/hr) and in man (0.39-6.22 x 10(-8) mol/kg/hr). Analysis of the responses was carried out by nonlinear regression using the logistic function. This allowed the data to be analyzed without making assumptions about the steepness of the curve which in man was almost twice that found in the dog (1.8:1). The ED50 in the dog was 0.26 +/- 0.029 x 10(-8) mol/kg/hr. The control dose-responses could be inhibited in a competitive manner by histamine-H2-receptor antagonists. Analysis of the control curve and three curves in the presence of increasing doses of antagonist was carried out by fitting all the curves simultaneously to calculate an in vivo ID50. In the dog, the antagonist was tiotidine (0.05, 0.1 and 0.2 x 10(-6) mol/kg/hr) and the ID50 was 0.012 +/- 0.002 x 10(-6) mol/kg/hr. In man, cimetidine (1.05, 2.10 and 4.2 x 10(-6) mol/kg/hr) was used to inhibit secretion. The calculated ID50 was 0.63 +/- 0.085 x 10(-6) mol/kg/hr. Comparison of the effect of cimetidine and tiotidine against both impromidine and histamine showed that the ID50 was the same for both stimulants. Impromidine proved to be a potent stimulant of gastric acid secretion acting via the H2-receptor to produce readily definable dose-response curves in the dog and in man.

Volume 225, Issue 1, pp. 186-190, 04/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics

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