ACTIVITY OF THE NEW HISTAMINE H-2-RECEPTOR ANTAGONIST ZOLANTIDINE AT CARDIAC AND GASTRIC H-2-RECEPTORS

The effect of the new histamine H-2-receptor antagonist zolantidine was studied in different cardiac and gastric H-2-receptor assays in comparison with ranitidine. Zolantidine (0.1-10 mu/mol/l) competitively antagonized the positive effects of histamine in the spontaneously beating guinea pig atria and in the electrically stimulated guinea pig papillary muscle (pA(2) values were 6.98 and 6.78, respectively). At the highest concentrations zolantidine also reduced basal heart rate and cardiac contractility. In the isolated rat gastric fundus zolantidine up to 100 mu mol/l did not modify histamine-induced acid secretion; it was similarly ineffective against dimaprit-induced acid secretion in the gastric fistula of conscious cats (up to 3 mu mol/kg i.v.) and against histamine in the anesthetized rat with lumen-perfused stomach (up to 30 mu mol/kg i.v.). In all these gastric secretory models ranitidine, as expected, antagonized histamine H-2-receptor-mediated responses, showing a potency comparable to that found in cardiac preparations (pA(2) values were 6.84, 6.38 and 6.78 in the atria, papillary muscle and gastric fundus, respectively). These data clearly showed that zolantidine is a very peculiar histamine H-2-receptor antagonist, capable of distinguishing between cardiac and gastric H-2-receptors; however, it still has to be elucidated whether this depends on a true heterogeneity in the histamine H-2-receptor population or on the physicochemical properties of the drug.