Study of the antisecretory and antiulcer mechanisms of a new indenopirydazinone derivative in rats.
The present study investigates the antisecretory and antiulcer mechanisms of a new indenopyridazinone derivative previously reported to inhibit gastric acid secretion in pylorus-ligated rats and to prevent gastric ulcerations induced by indomethacin or ethanol in the same animal species. The new compound was tested on the acid hypersecretion induced by histamine, pentagastrin and bethanechol in in vivo and in vitro experimental models. Furthermore, its influence on the mucosal layer adhering the gastric wall in indomethacin-treated rats was considered. Ranitidine was selected as a reference drug. The results obtained demonstrated that the new molecule, at variance with ranitidine, exerts antiulcer activity mainly enhancing the gastric mucosal integrity and simultaneously inhibiting the gastric acid hypersecretion evoked exclusively by cholinergic pulses. Therefore, an involvement of a neuronal rather than an effectorial mechanism has been suggested. Due to these mechanisms of action it clearly differentiates from ranitidine and its possible application in the peptic disease resistant to H2-blockers could be speculated.
Barocelli
E
E
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Parma, Italy.
Chiavarini
M
M
Ballabeni
V
V
Barlocco
D
D
Vianello
P
P
Dal Piaz
V
V
Impicciatore
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D018723:Bethanechol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin; D008297:Male; D051379:Mice; D009088:Mucoproteins / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D010418:Pentagastrin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011724:Pyridazines; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D006633:Histamine Antagonists; D009088:Mucoproteins; D018721:Muscarinic Agonists; D011724:Pyridazines; D018723:Bethanechol; D010418:Pentagastrin; D007213:Indomethacin