Cinitapride protects against ethanol-induced gastric mucosal injury in rats: role of 5-hydroxytryptamine, prostaglandins and sulfhydryl compounds

This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-H...

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Bibliographic Details
Published inPharmacology Vol. 54; no. 4; p. 193
Main Authors Alarcón-de-la-Lastra Romero, C, López, A, Martín, M J, la Casa, C, Motilva, V
Format Journal Article
LanguageEnglish
Published Switzerland 01.04.1997
Subjects
Animals
Benzamides - therapeutic use
Cell Survival - drug effects
Ethanol - toxicity
Gastric Mucosa - chemistry
Gastric Mucosa - drug effects
Gastric Mucosa - pathology
Prostaglandins - analysis
Prostaglandins - physiology
Rats
Rats, Wistar
Serotonin - administration & dosage
Serotonin - physiology
Sulfhydryl Compounds - analysis
Sulfhydryl Compounds - physiology
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Summary:This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-HT: 10 mg kg-1). The possible involvements of gastric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl compounds (SH) in the protection mediated by CNT were also examined. Intraperitoneal administration of CNT (0.50 and 1 mg kg-1), 30 min before ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg-1) also produced a significant increase in gastric mucosal levels of PGE2, but did not induce any significant changes in SH values. On the contrary, pretreatment with 5-HT worsened ethanol-induced erosions, however, did not affect gastric mucus secretion, glycoprotein content or PGE2 levels, although the non-protein SH fraction was significantly decreased. The present results demonstrate that the gastroprotective effects of CNT could be partly explained by a complex PG dependent mechanism. We suggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade and 5-HT1 receptor activation could be also involved.
ISSN:0031-7012