Watanabe K, Yano S, Yamamoto M, Kanaoka S
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Jpn J Pharmacol. 1993 Mar;61(3):229-36. doi: 10.1254/jjp.61.229.
We investigated the effects of cimetidine and famotidine on the acid secretory response to electrical vagal stimulation, bethanechol and histamine in the isolated mouse whole stomach preparation. The acid secretion elicited by electrical vagal stimulation at the position of the esophagus (10 Hz, 0.3 msec, 10 V for 5 min) was reproducible by repeated stimulation in each preparation, and it was abolished by tetrodotoxin, atropine and hexamethonium. This vagally stimulated acid secretion was abolished by cimetidine (3 mM), while it was only partly inhibited by famotidine (10-100 microM). Histamine (100 microM)-induced acid secretion was inhibited by cimetidine and famotidine, and the doses of these drugs required for complete inhibition were 3 mM and 10 microM, respectively. In contrast, bethanechol (10 microM)-induced acid secretion was slightly reduced by famotidine (1-100 microM), but markedly reduced by cimetidine (3 mM). In the guinea pig ileum, millimolar concentrations of cimetidine and famotidine shifted the dose-response curve of the contractile response to acetylcholine rightward. These findings suggest that the inhibitory effect of cimetidine on the vagally stimulated or bethanechol-induced acid secretion is elicited at least partly through mechanisms different from H2-antagonism.
