Potent and long-lasting action of lafutidine on the human histamine H2 receptor

Background/Aim: Based on animal models, lafutidine, a novel histamine H-2 receptor (H2R) antagonist, is reported to show potent and long-lasting antagonisms of histamine H2R-mediated effects. However, no reports have been published concerning its direct interaction with the human H2R. This study aims at characterizing its interaction with human H2R. Methods: Chinese hamster ovary cell lines stably expressing human H(2)Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [H-3]tiotidine binding and histamine-stimulated cAMP production were analyzed. The effects of preincubation with 2.78 x 10(-7) M of lafutidine or famotidine for 30 min on histamine-dependent CAMP production and [H-3]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the C-max of lafutidine (10 mg p.o.) and above the C-max of famotidine (20 mg p.o.). Results: Lafutidine inhibited [H-3]tiotidine binding and histamine-stimulated cAMP production as or more potently than famotidine. At higher concentrations lafutidine was more potent than famotidine. In addition, preincubation with 2.78 x 10(-7) M lafutidine, but not with 10(-5) M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. Conclusion: Lafutidine shows a potent and long-lasting antagonism on the human H2R. Copyright (C) 2001 S. Karger AG, Basel.