Antigastric and Antiulcerative Action of a New Proton Pump Inhibitor (IY-81233)

새로운 프로톤 펌프 억제제, IY-81233의 항위염과 항궤양작용

  • Kim, Seung-Hee (Department of Pharmacology, Center for Toxicological Research, Korea Food and Drug Administration) ;
  • Kim, Jeen (Department of Pharmacology, Center for Toxicological Research, Korea Food and Drug Administration) ;
  • Kang, Seog-Youn (Department of Pharmacology, Center for Toxicological Research, Korea Food and Drug Administration) ;
  • Lee, Song-Deuk (Department of Pharmacology, Center for Toxicological Research, Korea Food and Drug Administration) ;
  • Hong, Sung-Gul (Central Research Laboratory, Il Yang Pharmaceutical Company) ;
  • Kim, Dong-Yeun (Central Research Laboratory, Il Yang Pharmaceutical Company) ;
  • Moon, A-Ree (Duksung Women's University)
  • 김승희 (식품약품안전본부 독성연구소 약리부) ;
  • 김진 (식품약품안전본부 독성연구소 약리부) ;
  • 강석연 (식품약품안전본부 독성연구소 약리부) ;
  • 이송득 (식품약품안전본부 독성연구소 약리부) ;
  • 홍성걸 (일양약품 중앙연구소) ;
  • 김동연 (일양약품 중앙연구소) ;
  • 문애리 (덕성여자대학교 약학대학)
  • Published : 1996.09.01

Abstract

This study was designed to determine the effect of newly synthesized antiulcer agent, 5-pyrrolyl-6-halo-2-(pyridyl-2-methylthio)benzimidazole derivatives (IY-81233), on various experimental ulcers and on the secretion of prostaglandin $E_2(PGE_2)$ into the gastric lumen of rat. IY-81233 was previously reported to have a strong inhibitory effect on $H^+/K^$-ATPase and on gastric acid secretion in rats. Oral administration of IY-81233 at concentrations of 0.2, 2.0, and 20 mg/kg inhibited gastric lesions and duodenal ulcer induced by indomethacin, HCI-ethanol, water-immersion stress, cysteamine, and acetic acid in a dose dependent manner. Their IC$IC_{50}$ values were 3.4, 1.4, 0.8, 1.3, and 1.2 mg/kg, respectively. These results indicate that IY-81233 is a potent antiulcer agent although it is slightly less potent than omeprazole in healing of gastritis and ulcers. The secretion of $PGE_2$ into gastric lumen was also investigated in relation to the cytoprotective effect by IY-81233 in rats. The $PGE_2$ level was not changed significantly by an oral administration of IY-81233, suggesting that IY-81233 has little effect on the gastric protection. Therefore, it can be concluded that IY-81233 exerts prominent antiulcer activity by suppressing gastric acid secretion via an inhibition of a proton pump and not by protecting the gastrointestinal mucosa against various ulcerative stimuli.

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