Pharmacology of the novel H2 antagonist famotidine: in vitro studies

The novel antiulcer drug famotidine was found to be a potent and selective inhibitor of histamine H2 receptors. Its activity on different parameters involving H2 receptors was higher than that of other compounds of the family: pA2 values were 8.33, 7.86 and 7.83 in the guinea pig atria, guinea pig papillary muscle and isolated rat gastric secretion, respectively. Apart from quantitative differences, famotidine differed from the other compounds, since it caused a competitive antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The duration of the inhibitory action on the "in vitro" gastric secretion resembled that of cimetidine and ranitidine. Famotidine was highly effective (approximately 10 times as potent as ranitidine) also on the rat uterus (unsurmountable antagonism) and on the guinea pig gallbladder (pA2 value = 7.71). Famotidine was apparently devoid of non-specific effects concerning the gastrointestinal motility even at very high concentrations (10(-4) M). In this respect, famotidine appeared to be more selective than cimetidine and ranitidine at the H2 receptor level. The high potency, the peculiarity of the antagonism and the lack of side-effects on a number of isolated preparations, indicate this H2 antagonist as a very peculiar member of the group.