Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats:: A comparative study with omeprazole and lansoprazole

被引:12
作者
Takeuchi, K [1 ]
Konaka, A [1 ]
Nishijima, M [1 ]
Kato, S [1 ]
Yasuhiro, T [1 ]
机构
[1] Kyoto Pharmaceut Univ, Dept Pharmacol & Expt Therapeut, Kyoto 6078414, Japan
关键词
acid secretion; alkaline secretion; duodenal ulcer; H+/K+ ATPase inhibitor; mepirizole; pantoprazole;
D O I
10.1046/j.1440-1746.1999.01843.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Pantoprazole, 2-[(2-pyridylmethyl) sulphinyl] benzimidazole, is a new substituted benzimidazole that inhibits the parietal cell H+/K+-ATPase. Methods: In the present study, the anti-secretory and anti-ulcer activities of pantoprazole were compared with those of omeprazole and lansoprazole in rats. Results: Pantoprazole (0.3-3 mg/kg, p.o.) as well as omeprazole (1-10 mg/kg, p.o.) and lansoprazole (1-10 mg/kg, p.o.) dose-dependently decreased both basal acid secretion in pylorus-ligated rats and the stimulated acid secretion induced by mepirizole in acute fistula rats, and the effects of pantoprazole were more potent than those of omeprazole and lansoprazole, the ED50 values for the stimulated acid secretion being 0.8, 2.0 and 1.2 mg/kg, respectively. Neither of these drugs had any effect on duodenal HCO3- secretion. These pump inhibitors prevented the development of duodenal lesions in response to mepirizole in a dose-related manner, the ED50 values for pantoprazole, omeprazole and lansoprazole being 0.4, 2.0 and 1.3 mg/kg, respectively. Likewise, pantoprazole showed the healing promoting action on chronic duodenal ulcers induced by acetic acid, and this effect was also more potent when compared to omeprazole or lansoprazole. Conclusions: We conclude that pantoprazole exhibited both anti-ulcer and healing promoting effects on duodenal ulcers in rats, and the effects may be attributable to its potent anti-secretory action. Other pump inhibitors such as omeprazole and lansoprazole were almost equally effective as pantoprazole, yet this drug was most potent on the basis of ED50 values.
引用
收藏
页码:251 / 257
页数:7
相关论文
共 32 条
[1]  
BEKER JA, 1995, EUR J GASTROEN HEPAT, V7, P407
[2]  
Corinaldesi R, 1995, ALIMENT PHARM THERAP, V9, P667
[3]  
DEMEY C, 1994, INT J CLIN PHARM TH, V32, P98
[4]  
EKSTROM P, 1992, SCAND J GASTR S190, V27, P40
[5]   DUODENAL-ULCER - DISCOVERY OF A NEW MECHANISM AND DEVELOPMENT OF ANGIOGENIC THERAPY THAT ACCELERATES HEALING [J].
FOLKMAN, J ;
SZABO, S ;
STOVROFF, M ;
MCNEIL, P ;
LI, W ;
SHING, Y .
ANNALS OF SURGERY, 1991, 214 (04) :414-427
[6]  
GUGLER R, 1992, GASTROENTEROLOGY S, V102, P77
[7]   PANTOPRAZOLE IS SUPERIOR TO RANITIDINE IN THE TREATMENT OF ACUTE GASTRIC-ULCER [J].
HOTZ, J ;
PLEIN, K ;
SCHONEKAS, H ;
ROSE, K .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1995, 30 (02) :111-115
[8]   Capsaicin-sensitive sensory neurons are involved in bicarbonate secretion induced by lansoprazole, a proton pump inhibitor, in rats [J].
Inada, I ;
Satoh, H .
DIGESTIVE DISEASES AND SCIENCES, 1996, 41 (04) :785-790
[9]   (H+,K+)-ATPASE INHIBITING 2-[(2-PYRIDYLMETHYL)SULFINYL]BENZIMIDAZOLES .4. A NOVEL SERIES OF DIMETHOXYPYRIDYL-SUBSTITUTED INHIBITORS WITH ENHANCED SELECTIVITY - THE SELECTION OF PANTOPRAZOLE AS A CLINICAL CANDIDATE [J].
KOHL, B ;
STURM, E ;
SENNBILFINGER, J ;
SIMON, WA ;
KRUGER, U ;
SCHAEFER, H ;
RAINER, G ;
FIGALA, V ;
KLEMM, K ;
IFE, RJ ;
LEACH, CA .
JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (06) :1049-1057
[10]   SIMILARITIES AND DIFFERENCES IN THE PROPERTIES OF SUBSTITUTED BENZIMIDAZOLES - A COMPARISON BETWEEN PANTOPRAZOLE AND RELATED-COMPOUNDS [J].
KROMER, W .
DIGESTION, 1995, 56 (06) :443-454