Fedotozine reverses ileus induced by surgery or peritonitis: Action at peripheral κ-Opioid receptors

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Abstract

Background: Fedotozine is a peripheral opioid agonist. Its effects were assessed in experimental ileus in rats. Methods: Ileus was induced by abdominal surgery (laparotomy and cecum palpation) or peritonitis (acetic acid, intraperitoneally). Digestive motility was recorded by electromyography and gastrointestinal transit estimated using a51Cr-labeled test meal. Results: Surgery or peritonitis inhibited motility and migrating myoelectrical complexes for 2-3 hours. In both models, fedotozine (3 mg/kg, intravenously; 10 mg/kg, subcutaneously) restored a normal motility pattern. This action was reproduced by the κ-agonist, U-50, and 488H and was blocked by subcutaneous naloxone, naloxone-methiodide, or nor-binaltorphimine, a selective κ-antagonist. Peritonitis induced a 57% inhibition of gastric emptying and intestinal transit that was reversed by fedotozine (1-10 mg/kg, subcutaneously) or κ-agonists (U-50, 488H, bremazocine) but not δ-agonists (DPDPE, [d-Ala2]-deltorphin-II), whereas μ-aǵonists (morphine, fentanyl) potentiated ileus. Fedotozine restoration of transit was blocked by subcutaneous naloxone, naloxone-methiodide, or nor-binaltorphimine but not by intracerebroventricular naloxone. Fedotozine was inactive up to 300 μg/rat when given intracerebroventrically or intrathecally. Conclusion: Fedotozine reverses experimental ileus via an action at peripheral κ-opioid receptors. © 1993.

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APA

Rivière, P. J. M., Pascaud, X., Chevalier, E., Le Gallou, B., & Junien, J. L. (1993). Fedotozine reverses ileus induced by surgery or peritonitis: Action at peripheral κ-Opioid receptors. Gastroenterology, 104(3), 724–731. https://doi.org/10.1016/0016-5085(93)91007-5

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