Action of the new H2-antagonist, DA 4577, on different in vitro and in vivo preparations.

Abstract

The new H2-antagonist, 4(5)-(4- isopropylaminomethyleniminophenyl )-imidazole (compound marked DA 4577), was tested for its activity on different in vitro preparations and also in the conscious cat. Its effect was compared with that of some new H2 antagonists. Two sets of experiments were performed: in the first, concerning the specific H2-receptor antagonism, DA 4577 was found to be extremely potent on the guinea-pig papillary muscle and on the human atrium stimulated by histamine (pA2 = 8.24 and 8.60 respectively). Compound DA 4577 was also found very active in inhibiting histamine-induced acid secretion from the isolated rat fundus (pA2 = 7.37) and on the dimaprit-induced gastric secretion in conscious gastric fistula cats (ID50 = 0.39 mumol kg-1 h-1). In the second set of experiments, concerning effects independent of the H2-receptor blockade (side effects of the molecule), compound DA 4577 was found to be devoid of negative inotropic effect on the human atrium in the absence of histamine stimulation; in this respect it behaved like cimetidine or ranitidine but unlike oxmetidine which showed a constant negative inotropic effect even at concentration 10 times lower than those of DA 4577. Furthermore DA 4577 was ineffective in modifying gastrointestinal motility in vitro in concentrations up to 3 X 10(-4) M, conversely from ranitidine (which stimulated motility) and oxmetidine (which inhibited motility). On the whole DA 4577 appeared to be a very potent and selective H2 antagonist which, unlike other members of the family, is devoid of non-specific effect on human atrium and on motility of the gastrointestinal tract of different animal species.