Pharmacological interactions between ranitidine, cimetidine, metiamide and tiotidine at histamine H2-receptor sites in guinea-pig atria.

Cumulative concentration-response curves to histamine or dimaprit were constructed on guinea-pig isolated right atria and agonist dose-ratios were determined following addition of ranitidine, cimetidine, metiamide or tiotidine alone or a combination of any two of these H2-receptor blocking drugs. The observed histamine or dimaprit dose-ratios for combinations of any two of the H2-antagonists tested were consistent with results predicted from the equation, DR1+2 = DR1 + DR2 - 1, for two antagonists competing for the same receptor sites. Therefore we conclude that all four H2-antagonists compete for the same histamine H2-receptor.