Cardiac effects of the new H2-receptor antagonists.

A series of new H2-receptor antagonists were tested for their effects on different isolated heart preparations. In the guinea-pig atria and papillary muscle the inhibitory effect on histamine H2-receptors was evaluated. In the perfused rabbit heart and in strips of human atria the effect of the H2-antagonists on the spontaneous or electrically-stimulated contractions was evaluated. In the first two preparations some main quantitative differences were pointed out, tiotidine and compound SKF 93479 being the most potent antagonists, cimetidine, metiamide and ranitidine the less effective. In the rabbit heart and in human atria results were quite different: cimetidine and ranitidine were virtually ineffective up to the maximum concentration tested (3 x 10(-3) M), oxmetidine and compound SKF 93479 had a negative inotropic and chronotropic effect starting from concentrations of 3 x 10(-6)-10(-5) M. On the basis of the behaviour of other compounds endowed with negative cardiac effects (propranolol, anaesthetic-like compounds, verapamil) and of that of compounds capable of counteracting the effect of oxmetidine (increased concentration of calcium ions and isoproterenol) it was hypothesized that oxmetidine may interfere in the transport of calcium ions. Our data emphasize the importance of the different structure of the H2-antagonists in determining non-specific effects absolutely independent of the primary action that is the H2-receptor blockade.