Some in vitro and in vivo actions of the new histamine H2-receptor antagonist, ranitidine.

1 Ranitidine has been investigated as an antagonist of the H2-receptor-mediated responses to histamine of guniea-pig atrium and rat uterus in vitro and as an inhibitor of gastric acid secretion in the rat. 2 Ranitidine competitively antagonized histamine-induced increases in contraction frequency of the guinea-pig isolated rat atrium. Ranitidine had a pA2 of 7.2 and was 7.9 and 4.5 times more potent than metiamide and cimetidine respectively. 3 Ranitidine competitively antagonized histamine-induced relaxations of the rat isolated uterine horn. Ranitidine had a pA2 of 6.95 and was 3.6 and 5.9 times more potent than metiamide and cimetidine respectively. 4 Ranitidine, even at high concentrations, did not affect responses of the guinea-pig isolated atrium or rat isolated uterus to (-)-isoprenaline. Similarly it was without effect on either histamine or bethanechol-induced contractions of guinea-pig isolated ileum. 5 Ranitidine inhibited histamine- and pentagastrin-induced gastric acid secretion in the perfused stomach preparation of the anaesthetized rat. Ranitidine was 5.2 and 7.0 times more potent on a molar basis than metiamide and cimetidine respectively, as an inhibitor of histamine-induced gastric acid secretion. 6 It is concluded that ranitidine is a potent, competitive and selective antagonist of histamine at H2-receptor sites and and effective inhibitor of gastric acid secretion in vivo.