Inhibitory cholinergic effects of esaprazole on gastric secretion and plasma gastrin levels in the dog.
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.
Blandizzi
C
C
Institute of Medical Pharmacology, University of Pisa, Italy.
Mengozzi
G
G
Intorre
L
L
Natale
G
G
Soldani
G
G
Del Tacca
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000097:blood / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D005755:Gastrins; D010879:Piperazines; C042123:esaprazole