Further observations on the motor activity of some new histamine H2-receptor antagonists on the digestive system

Some new H2-receptor antagonists were tested for their motor effects on the rat lower oesophageal sphincter, on the guinea pig ileum and on the guinea pig gall bladder. Two of these compounds, SKF93479 and DA4577, were found to be virtually inactive despite the fact that they are the most potent antagonists of the H2-receptors so far described. Ranitidine possessed a stimulatory effect on all the preparations examined and its mechanism of action was shown to involve the cholinergic system. Conversely oxmetidine exerted an inhibitory effect on the contractions produced by a variety of spasmogenic compounds. All of these observations, together with other data from our laboratory, seem to suggest that H2-receptors do not play an important role in the regulation of the motility of the digestive system. Moreover our data emphasize the fact that the motor effects of the H2-antagonists are connected with single molecules rather than with the entire class, and therefore represent side-effects of these compounds independent of the H2-receptor blockade.