The κ agonist fedotozine (cas 123618-00-8) modulates colonic distention-induced inhibition of gastric motility and emptying in dogs

Add time:08/11/2019    Source:sciencedirect.com

Background/Aims: Gastric motor disturbances, associated with a delay in gastric emptying, occur in patients with the irritable bowel syndrome. The influence of fedotozine (cas 123618-00-8) and κ agonists on the cologastric reflex produced by nonpainful colonic distention was evaluated in conscious dogs. Methods: Colonic distention was applied in dogs fitted with either strain gauges or gastric cannula to assess its influence on gastrointestinal motility and gastric emptying, respectively. Results: Colonic distention delayed the occurrence of gastric migrating motor complex by 141%, an effect blocked by intravenous fedotozine, U 50 488 (25 and 50 μg/ kg), and hexamethonium (0.5 mg/kg) but not by d-Ala2, N-methyl, Phe4, Gly5-ol enkephalin (1, 5, and 10 μg/ kg), granisetron (50 and 100 μg/kg), or bretylium to-sylate (5 mg/kg). Nor-binaltorphimine hydrochloride (1 mg/kg intravenously) eliminated the suppressive action of fedotozine. Colonic distention reduced the 1-hour gastric emptying of solids by 40.1%, an effect blocked by fedotozine and U 50 488 (50 and 100 μg/ kg); nor-binaltorphimine hydrochloride (1 mg/kg) antagonized the blocking effect of fedotozine. Conclusions: Fedotozine acts through κ receptors to block the colonic distention-induced delay on gastric motility and emptying. The cologastric reflex involves nicotinic ganglionic receptors but not adrenergic pathway and 5-hydroxytryptamine 3 receptors.

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