Blandizzi C, Mengozzi G, Intorre L, Natale G, Soldani G, Del Tacca M
Institute of Medical Pharmacology, University of Pisa, Italy.
Pharmacology. 1993 Apr;46(4):231-40. doi: 10.1159/000139050.
The effects of esaprazole, a novel antiulcer drug, on gastric acid secretion and plasma gastrin levels were investigated in dogs provided with a gastric fistula or Heidenhain pouch. Esaprazole affected in a different extent the tests performed on dogs with a gastric fistula. The greatest inhibitory effect was obtained against 2-deoxy-D-glucose-induced acid output and gastrin release. An intermediate inhibition by esaprazole was detected on bethanechol-evoked secretion, and the lowest activity was found versus histamine-stimulated secretion. All these responses were strongly inhibited by the antimuscarinic drug pirenzepine used as reference drug. Moreover, both esaprazole and pirenzepine prevented the acid secretory response to a test meal in dogs with a Heidenhain pouch, without significantly affecting plasma gastrin levels. The present results suggest that the depressant action of esaprazole on gastric secretion depends on its peripheral anticholinergic activity, consisting of a partial blockade of acid output and a main reduction of vagally mediated gastrin release. On the basis of these findings, the antiulcer activity of esaprazole might be in part ascribed to its inhibitory effects on gastric secretion.
在设有胃瘘或海登海因小胃的犬中，研究了新型抗溃疡药物埃索美拉唑对胃酸分泌和血浆胃泌素水平的影响。埃索美拉唑对患有胃瘘的犬所进行的试验有不同程度的影响。对2-脱氧-D-葡萄糖诱导的酸分泌和胃泌素释放产生的抑制作用最大。检测到埃索美拉唑对氨甲酰甲胆碱诱发的分泌有中等程度的抑制作用，而对组胺刺激的分泌活性最低。用作参比药物的抗毒蕈碱药物哌仑西平强烈抑制所有这些反应。此外，埃索美拉唑和哌仑西平均可防止海登海因小胃犬对试餐的酸分泌反应，且对血浆胃泌素水平无显著影响。目前的结果表明，埃索美拉唑对胃分泌的抑制作用取决于其外周抗胆碱能活性，包括对酸分泌的部分阻断和对迷走神经介导的胃泌素释放的主要减少。基于这些发现，埃索美拉唑的抗溃疡活性可能部分归因于其对胃分泌的抑制作用。
