Potent and Long-Lasting Action of Lafutidine on the Human Histamine H2 Receptor

Background/Aim: Based on animal models, lafutidine, a novel histamine H2 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 H2Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [3H]tiotidine binding and histamine-stimulated cAMP production were analyzed. The effects of preincubation with 2.78 × 10–7M of lafutidine or famotidine for 30 min on histamine-dependent cAMP production and [3H]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the Cmax of lafutidine (10 mg p.o.) and above the Cmax of famotidine (20 mg p.o.). Results: Lafutidine inhibited [3H]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 × 10–7M lafutidine, but not with 10–5M 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.