PMID- 11304936
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20181130
IS  - 0004-4172 (Print)
IS  - 0004-4172 (Linking)
VI  - 51
IP  - 3
DP  - 2001
TI  - Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid 
      secretion in vitro and in vivo.
PG  - 204-13
AB  - The inhibitory effects of IY-81149 (2-[[(4-methoxy-3-methyl)-2- 
      pyridinyl]methyl-sulfinyl]-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 IC50 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 14C-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) mol/l 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 IY-81149 
      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 ED50 of IY-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 IY-81149. 
      The histamine induced increase of acid output in the Heidenhain pouch dog was 
      blocked by 71% 150 min after oral administration of enteric-coated IY-81149 at a 
      dose of 3 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.
FAU - Kwon, D
AU  - Kwon D
AD  - Department of Pharmacology and Toxicology, Il Yang Central Research Institute, 
      Kyunggi-Do, Korea.
FAU - Chae, J B
AU  - Chae JB
FAU - Park, C W
AU  - Park CW
FAU - Kim, Y S
AU  - Kim YS
FAU - Lee, S M
AU  - Lee SM
FAU - Kim, E J
AU  - Kim EJ
FAU - Huh, I H
AU  - Huh IH
FAU - Kim, D Y
AU  - Kim DY
FAU - Cho, K D
AU  - Cho KD
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Arzneimittelforschung
JT  - Arzneimittel-Forschung
JID - 0372660
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Sulfoxides)
RN  - 01704YP3MO (Aminopyrine)
RN  - 776Q6XX45J (ilaprazole)
RN  - 820484N8I3 (Histamine)
RN  - EF0NX91490 (Pentagastrin)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles
MH  - Aminopyrine/metabolism
MH  - Animals
MH  - Anti-Ulcer Agents/*pharmacology
MH  - Benzimidazoles/*pharmacology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Gastric Acid/*metabolism
MH  - Gastric Mucosa/drug effects/metabolism
MH  - Histamine/pharmacology
MH  - In Vitro Techniques
MH  - Male
MH  - Omeprazole/pharmacology
MH  - Pentagastrin/pharmacology
MH  - *Proton Pump Inhibitors
MH  - Rabbits
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stomach/drug effects
MH  - Sulfoxides/*pharmacology
EDAT- 2001/04/18 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/04/18 10:00
PHST- 2001/04/18 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/18 10:00 [entrez]
AID - 10.1055/s-0031-1300026 [doi]
PST - ppublish
SO  - Arzneimittelforschung. 2001;51(3):204-13. doi: 10.1055/s-0031-1300026.