Effect of FRG-8813, a New-Type Histamine H₂-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats

Abstract

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (±)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H₂-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p.o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days’ administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy.

Lafutidine Changes Levels of Somatostatin, Calcitonin Gene-Related Peptide, and Secretin in Human Plasma

“…9,32) It also treats gastrointestinal functions by regulating gastrointestinal motility. 10,11) In this study, gut-regulated peptide (somatostatin, CGRP, gastrin, secretin, and motilin) levels, which regulate gastrointestinal function, were examined to study their relation with lafutidine.…”

“…10,11) Our studies of gut hormone levels add one viewpoint on mechanism of lafutidine. In conclusion, ingestion of lafutidine causes changes in the plasma levels of somatostatin-IS, CGRP-IS, and secretin-IS.…”

“…10,11) Its effects on gastrointestinal function are mainly regulated by hormonal and neuronal mechanisms, however, the mechanism is not clear. Therefore, we examined the plasma levels of brain-gut peptides which regulate gastrointestinal function.…”

Possible Involvement of Host Defense Mechanism in the Suppression of Rat Acute Reflux Esophagitis by the Particular Histamine H2 Receptor Antagonist Lafutidine

“…These effects of lafutidine differ from those of conventional H 2 RAs. In fact, compared with famotidine, lafutidine reportedly improved the quality of gastric ulcer healing in rats [9,10] and humans [11]. Furthermore, lafutidine had a high endoscopic healing rate and was associated with a rapid improvement of symptoms in a randomized, double-blind, controlled study in which lafutidine and famotidine were evaluated for their efficacy and safety in patients with mild GERD, raising the possibility that a mucosa-protective effect may contribute to therapy for GERD patients [12].…”

Interdisciplinary review for correlation between the plant origin capsaicinoids, non-steroidal antiinflammatory drugs, gastrointestinal mucosal damage and prevention in animals and human beings

“…We also participated in the GI capsaicin research in animal experiments from 1980 (Mózsik et al 1997a, b, c). Recently, the new drug, lafutidine, was processed in the medical treatment of GI mucosal damage (Aijoka et al 2000(Aijoka et al , 2002Onodera et al 1999Onodera et al , 2002Takeuchi 2006). The lafutidine is a H2R blocking compound together with typical capsaicin actions at the target organ.…”