EFFECT OF FEDOTOZINE ON THE CARDIOVASCULAR PAIN REFLEX INDUCED BY DISTENSION OF THE IRRITATED COLON IN THE ANESTHETIZED RAT

The effect of fedotozine was evaluated in a model of colonic hypersens ibility to balloon distension in anesthetized rats. Acetic acid (0.6%, intracolonically) significantly enhanced the hypotension reflex respo nse to colonic distension (P < 0.05). At a noxious pain pressure (75 m m Hg), fedotozine ethoxy)benzyloxymethyl]N,N-dimethyl-n-propylamine) h ad no effect at 0.6 and 1 mg/kg i.v. in saline-treated rats and higher doses were required to produce antinociception (ED(50) = 2.57 mg/kg i .v.). By contrast, fedotozine at 0.6 and 1 mg/kg i.v. displayed 38 and 54% antinociception (P < 0.05) respectively, in acetic acid-treated a nimals, leading to a decrease in its ED(50) (1.15 mg/kg i.v.). Similar results were obtained with lidinyl)-cyclohexyl]benzo[b]-thiophene-4-a cetamide (PD-117,302), a kappa-opioid receptor agonist, while the anti nociceptive action of morphine and a kappa-opioid receptor agonist, l- N-(2-[1-pyrro-lidinyl]cyclohexyl)benzenacetamide ((+/-)-U-50,488H), wa s identical in control and acetic acid-treated animals. Nor-binaltorph imine, a selective kappa-opioid receptor antagonist, reversed the enha nced antinociceptive activity of fedotozine and PD-117,302. It is conc luded that acetic acid induces colonic hypersensibility to painful mec hanical stimuli and that some but not all kappa-opioid receptor ligand s can have enhanced efficacy in this pathological situation.