Positive inotropic activity of the novel histamine H2-receptor agonist, amthamine, on the human heart in vitro.

1. We tested the novel thiazole derivative, amthamine, for its ability to stimulate histamine H2-receptors in the human myocardium. 2. Experiments were carried out on isolated, electrically-driven pectinate muscle segments, excised from atrial appendages of patients undergoing corrective heart surgery. 3. Amthamine (0.3-100 microM) induced a positive inotropic activity, resembling histamine in terms of potency and efficacy. In comparison, impromidine was 10-30 times more active than histamine and amthamine, but its maximum effect was significantly lower, while dimaprit was as effective as histamine, but 10 times less potent. 4. The selective histamine H2-blocker, famotidine antagonized in a competitive fashion the amthamine-induced positive inotropic effect. pA2 value of famotidine against amthamine (7.21 +/- 0.45) was close to that measured against histamine (6.88 +/- 0.31) in the same conditions. 5. The effect of amthamine was not modified by beta-adrenoceptor blockade, excluding direct or indirect sympathomimetic activities of the compound. 6. These data provide evidence that amthamine is a selective and full acting histamine H2-receptor agonist in the human heart in vitro.