H2-receptor antagonism by a novel compound IT-066 assessed from [14C]aminopyrine accumulation in rabbit parietal cells.

The H2-receptor antagonistic activities and properties of IT-066 were investigated in rabbit isolated gastric mucosal cell and were compared with those of famotidine and cimetidine. IT-066 inhibited dose dependently the histamine-stimulated [14C]aminopyrine ([14C]AP) accumulation in parietal cells. The antagonism was unsurmountable. The inhibitory action of IT-066 was enhanced by lengthening of its incubation time with the cells. IT-066 following 30 min preincubation with the parietal cells showed 32 and 1560 times the activity of famotidine and cimetidine, respectively, as an inhibitor of [14C]AP accumulation. The inhibitory activity of IT-066 on the histamine effect remained after repeated washing of the cells while with famotidine and cimetidine the response to histamine was restored after washout of the drugs from the cells. These data indicate that the antagonism of IT-066 on histamine H2-receptors is high and is unsurmountable in the isolated parietal cell model.