Effect of pibutidine hydrochloride (IT-066), a novel histamine H_2 -receptor antagonist, on the healing of chronic gastric ulcers

IT-066 has a potent and long lasting antisecretory effect. We examined the effect of IT-066 on the healing of chronic gastric ulcer in rats and Mongolian gerbils. Four days after the induction of acetic acid ulcer, IT-066 (1-10 mg/kg) was administered orally twice a day for 1 or 2 weeks. The ulcer healing was significantly accelerated by the treatment of IT-066. Histologically, the healing index and the regenerated mucosa index were improved. The healing of acetic acid ulcer was delayed by the 3-weeks treatment of indomethacin (2 mg/kg, s.c.), and IT-066 inhibited the delayed healing. IT-066 also prevented the recurrence of ulcer induced by the 18-days treatment of hydrocortisone (20 mg/kg, s.c.). Moreover, IT-066 (0.3-3 mg/kg, p.o.) increased the mitogenic activity of gastric juice. In Mongolian gerbils, Hellcobacterpylori infection delayed the healing of acetic acid ulcer. IT-066 accelerated the healing and potentiated the effect of clarithromycin. These results suggest that IT-066 has a curative effect on the chronic gastric ulcer, and that the mitogenic activity may be involved in its curative effect.