Effects of a Proton Pump Inhibitor, AG-1749 (Lansoprazole), on Reflux Esophagitis and Experimental Ulcers in Rats.

Abstract

ABSTRACT-The effects of (±)-2- [[[3-methyl-4-(2,2,2-trifluoroethoxy-2-pyridyljmethyl]-sulfinyl]-1H-benzimidazole (lansoprazole, AG-1749) and famotidine on various experimental ulcers in rats were compared. AG-1749 inhibited reflux esophagitis; gastric lesions induced by water-immersion stress, aspirin or ethanol; and duodenal ulcers induced by cysteamine or mepirizole in a dose-dependent manner: the ID50 values were 0.7, 2.4, 0.7, 8.5, 1.1 and 0.3 mg/kg, p.o. or i.d., respectively. Famotidine inhibited reflux esophagitis with an ID50 value of 12.9 mg/kg, but did not cause 50% inhibition of ethanol-induced gastric lesions even at 100 mg/kg, although it showed almost the same or a little stronger potency on other experimental ulcers: ID50 values were 0.3 -1.4 mg/kg. Significant aggravation of ethanol-or water-immersion stress-induced lesions was observed in rats given famotidine at 30 mg/kg twice daily for 4 days, but not in rats given AG-1749 at 10 mg/kg twice daily. Administration of AG-1749 for 14 consecutive days markedly accelerated the healing of acetic acid-induced gastric and duodenal ulcers, and the healing effect was significant at 10 and 30 mg/kg/day, p.o. Famotidine also accelerated the healing of ulcers, but its potency was less than that of AG-1749. The results of this study indicate that although AG-1749 is slightly less potent than famotidine in inhibiting acutely induced gastroduodenal lesions, this agent is superior to famotidine in promoting the healing of ulcers and in inhibiting reflux esophagitis and ethanol-induced gastric lesions.

D-002 Ameliorates Histological Changes in Rats with Bile Reflux-Induced Esophagitis

“…[29] DER-induced esophagitis in rats DER was surgically induced in rats according to Hashimoto 2012. [30] Solid foods was withdrawn 1 day before and for 1 day after surgery.…”

Experimental model of gastroesophageal reflux in rats

“…Ferguson 19 developed a model in rats and other animal species, by occluding the duodenum below the pylorus, and associating with the administration of histamine. Nakamura et al 5 , Inatomi 6 and Omura 4 developed experimental models of acid and chronic reflux esophagitis by occluding the rumen and obstructing the pylorus. The model developed by Nakamura et al 5 had the disadvantage of causing extrinsic (mechanical) gastric obstruction.…”

“…Experimental models of GERD are important to study the action of the acid and alkaline juices, as well as to evaluate the therapeutic efficacy of drugs and surgical techniques. The closure of the pylorus and of the rumen helped studying reflux esophagitis in rats, according to the models developed 4,5,6 . The authors also tested the therapeutic efficacy of different esophageal mucosa protective drugs.…”

Pharmacological Profile of Gastric Mucosal Protection by Marmin and Nobiletin from a Traditional Herbal Medicine, Aurantii Fructus Immaturus

“…On the contrary, gastric acid plays a cru cial role in the development of the aspirin-induced gastric lesions (16). The gastric lesion induced by ethanol was markedly prevented by drugs increasing the defensive fac tors, while the lesion induced by aspirin was prevented by drugs inhibiting the aggressive factors such as gastric acid (17,18). Our previous studies have also shown that sucral fate, 16,16-dimethyl prostaglandin E2 and cetraxate, drugs increasing the defensive factors, effectively inhibit ed ethanol-induced gastric lesions (17,19).…”