Inhibitory effect of cimetidine, an antagonist of histamine H2-receptor, on gastric acid secretion in isolated frog stomach and in anesthetized young chicken.

Gastric antisecretory effect of a new histamine H2-receptor antagonist, N"-cyano-N-methyl-N'-[2-T5-methyl-imidazol-4-yl)-methylthioethyl]guanidine (cimetidine), was studied in isolated bullfrog gastric mucosa and in anesthetized young chicken preparation with acute gastric fistulae. Cimetidine inhibited dose-dependently the secretory responses of frog gastric mucosa to histamine, and parallel shift of the concentration-response curve of histamine by cimetidine indicated the competitive character of the antagonism. However, cimetidine inhibited the stimulatory action of methacholine and gastrin as well as histamine on gastric secretion. Cimetidine pretreatment protected the histamine sensitivity of gastric mucosa from the irreversible blocking action of dibenamine. It was also found in the chicken preparation that cimetidine strongly depressed the maximal acid secretory response to histamine as well as to tetragastrin or methacholine. These results may afford the evidence indicating the specific action of cimetidine and the involvement of histamine-related mechanism in the action of the other two secretagogues.