Fedotozine blocks hypersensitive visceral pain in conscious rats: action at peripheral κ-opioid receptors

Pathophysiology and treatment of functional dyspepsia

“…82,83 In a small study, amitriptyline was found to improve symptoms of functional dyspepsia without an effect on gastric sensitivity. 84 Fedotozine, a peripherally acting kappa opioid receptor agonist, influences visceral sensitivity, 85,86 and it has been shown to increase discomfort thresholds to gastric distension in healthy volunteers. 87 However, development of this drug has not been continued.…”

Effects of Tachykinin NK1 Receptor Antagonists on the Viscerosensory Response Caused by Colorectal Distention in Rabbits

“…Abdominal contractions induced by colorectal distention in rats have been used to quantify visceral perception and to assess therapeutic agents for functional bowel disorders such as IBS (Langlois et al, 1997). Because this response is attenuated by morphine, colorectal distention seems to act as a nociceptive stimulus to organs, leading to abdominal contractions (Ness and Gebhart, 1988).…”

“…Although the mechanism underlying this hypersensitivity is not fully understood, previous infection, inflammation, and/or psychological stress have been associated with the bowel dysfunction observed in IBS (Gwee et al, 1996;Accarino et al, 1997). Langlois et al (1997) found that colorectal hypersensitivity could be induced by intracolorectal treatment with 0.6% acetic acid solution in rats. In the present study, we used 0.8% acetic acid solution to induce colorectal hypersensitivity.…”

“…The balloon was rapidly inflated with air to a pressure of 30 mm Hg, and this pressure was maintained for 10 min. Colorectal irritation was performed according to the method of Langlois et al (1997) with minor changes. Acetic acid solution (0.8%, 4 ml, 24 ml/min) was applied to the colorectal region through a silicone catheter (o.d., 3 mm; i.d., 2 mm) inserted 2 to 8 cm in from the anal verge.…”

Centrally acting agents and visceral sensitivity

“…The observation that fedotozine was inactive against visceral pain induced by colonic distension when administered by the intracerebroventricular route suggests that its action is peripheral. 41 In another study, fedotozine was shown to be more active when administered by intrathecal than by intravenous routes in a study where neuronal responses to colorectal distension were recorded in the dorsal horn of the lumbosacral spinal cord, suggesting that the drug does have a central action at least at the level of the spinal cord. 43 Thus clear evidence of a central effect of either of these two opiate receptor agonists has yet to be obtained.…”