Antagonistic activity of tiotidine and ranitidine on guinea-pig and rabbit atria.

Isolated, spontaneously beating atrial pairs from rabbits and guinea-pigs were used to determine and to compare the activity of ranitidine and tiotidine as antagonists of histamine stimulated chronotropic activity. Ranitidine produced a classical competitive, reversible antagonism of histamine effects with a pA2 in rabbit atria of 8.2. In contrast, tiotidine produced both a dextral shift of the log dose-response curve, as well as a previously unreported suppression in the maximal response produced by histamine. In accordance with receptor theory, this type of activity represents a dualistic antagonism of histamine chronotropic responses.