IN-VITRO CARDIAC PHARMACOLOGY OF THE NEW HISTAMINE H-2-RECEPTOR AGONIST AMTHAMINE - COMPARISONS WITH HISTAMINE AND DIMAPRIT

The cardiac activity of the novel histamine H-2-receptor agonist amtha mine was investigated in a variety of isolated heart preparations from guinea pigs and humans and in the isolated rabbit aorta. Amthamine ca used an increase in the sinus rate of spontaneously beating guinea-pig atria (pD2 = 6.72) and in the contractility of the electrically drive n guinea-pig papillary muscle (pD2 = 6.17) and of the human atrium (pD 2 = 5.38). In all these systems, amthamine behaved as a full agonist w ith a potency comparable to or slightly higher than that of histamine and 10 times higher than that of dimaprit. The positive effects of amt hamine were competitively antagonized by ranitidine which had pA2 valu es (6.46 and 6.25 in the guinea-pig atria and papillary muscle, respec tively) comparable with those calculated against histamine and dimapri t. In the isolated rabbit aorta amthamine was devoid of H-1-mediated a ctivities up to 3 x 10(-4) M. These results indicate that amthamine is a potent and selective histamine H-2-receptor agonist which can be co nsidered a valuable tool for investigating H-2-receptor mediated effec ts in cardiac tissues.