Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo
- Authors
- Kwon, D; Chae, JB; Park, CW; Kim, YS; Lee, SM; Kim, EJ; Huh, IH; Kim, DY; Cho, KD
- Issue Date
- Jan-2001
- Publisher
- ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN
- Keywords
- antiulcer drug; CAS 73590-58-6; CAS 172152-36-2; TY-81149, dog, gerenal pharmacology, rat; 2-[[(4-methoxy-3-methyl)-2-pyridinyl]methylsulfinyl]-5-(1H-pyrol-1-yl)-1 H-benzimidazole; omeprazole; proton pump inhibitors
- Citation
- ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH, v.51, no.3, pp 204 - 213
- Pages
- 10
- Journal Title
- ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH
- Volume
- 51
- Number
- 3
- Start Page
- 204
- End Page
- 213
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/47281
- ISSN
- 0004-4172
- Abstract
- The inhibitory effects of IY-81149 (2-[[(4methoxy-3-methyl) -2-pyridinyl] methylsulfinyl] -5-(1H-pyrol-1-yl)-1H-benzimidazole, CAS 172152-36-2), a newly developed proton pump inhibitor (PPI) on gastric acid secretion were investigated in vitro and in vivo. In rabbit parietal cell preparation, IY-81149 irreversibly inhibited H+/K+-ATPase in dose-dependent manner With an ICS, of pump inhibitory activity of 6.0 x 10(-6) mol/l and that of omeprazole (CAS 73590-58-6) was 1 x 10(-4) mol/l at pH 7.4. On cumulation of C-14-aminopyrine in histamine stimulated parietal cells, the IC50 of IY-81149 was 9.0 x 10(-9) mol/l and that of omeprazole was 1.9 x 10(-8) mol/l. The inhibition rates of IY-81149 and omeprazole at a concentration of 1 x 10-9 moU1 in human parietal cells were 137 % and 64 %, respectively. In pylorus-ligated rats, IY-81149 showed a 2-3 times stronger inhibitory activity than omeprazole against gastric acid secretion. The ED50 of IY-81149 and omeprazole administered intraduodenally was 1.6 mg/kg and 3.8 mg/kg, In the case of oral administration, the ED50 of IY81149 and omeprazole was 1.94 mg/kg and 5.64 mg/kg, respectively. But after 24 h administration, the anti-secretory activity of IY-81149 was lower than that of omeprazole at all doses tested. In anesthetized rats, IY-81149 dose-dependently increased gastric pH which was lowered by histamine infusion. In the case of i.v. injection, the ED50 of IY-81149 and omeprazole was 1.2 and 1.4 mg/kg and in the case of i.d. administration, the ED50 of IY-81149 and omeprazole was 3.9 and 4.1 mg/kg, respectively. IY-81149 also significantly inhibited pentagastrin-stimulated gastric secretion. Its ED50 was 2.1 mg/kg and that of omeprazole was 3.5 mg/kg with i.d. administration. In the case of i.v. injection, IY-81149 was equipotent to omeprazole. IY-81149 also inhibited gastric acid secretion strongly in fistular rats. The EDS, of TY-81149 administered intraduodenally was 0.43 mg/kg and that of omeprazole was 0.68 mg/kg. In Heidenhain pouch dogs, the acid output was completely blocked at 0.3 mg/kg, 135 min after i.v. administration. Omeprazole showed a similar effect as IY81149. The histamine induced increase of acid output in the Heidenhain pouch dog was blocked by 71 % 150 min after oral administration of enteric-coated IV-81149 at a dose of S mg/kg, and omeprazole showed similar effects. In conclusion, IY-81149 revealed the characteristics as a strong proton pump inhibitor, and its potency against gastric acid secretion was superior to that of the reference drug, omeprazole.
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