Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the recurrence of gastric ulcer after healing by drug treatment in rats.
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 H(2)-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.
Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
H
H
Ajioka
H
H
Miyake
N
N
Matsuura
D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D016099:Endoscopy, Gastrointestinal; D015738:Famotidine / Q000008:administration & dosage / Q000627:therapeutic use; D005745:Gastric Acidity Determination; D005755:Gastrins / Q000097:blood; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017063:Outcome Assessment, Health Care; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D055502:Secondary Prevention; D013276:Stomach Ulcer / Q000097:blood / Q000473:pathology / Q000517:prevention & control*
D000081:Acetamides; D005755:Gastrins; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D015738:Famotidine