EFFECT OF THE KAPPA-AGONIST FEDOTOZINE ON PERCEPTION OF GASTRIC DISTENSION IN HEALTHY HUMANS

Background and Aim: Gastric hypersensitivity to mechanical distension has been observed in functional dyspepsia, but no drug is available th at specifically acts on gastric afferent pathways to decrease gastric nociception. The aim of this study was to assess the effect of fedotoz ine, a synthetic ligand for peripheral kappa receptors, on human gastr ic sensitivity. Methods: Twenty-seven healthy volunteers were randomiz ed to receive either fedotozine (30 mg t.d.s.) or a placebo, for 7 day s. On day 7, the effects of fedotozine were tested on discomfort thres hold and gastric compliance during graded isobaric and isovolumic dist ensions. In 16 of these subjects, the effect of this drug was tested o n somatic sensitivity. In 10 other healthy volunteers the effect of fe dotozine on gastric distension-induced inhibition of the RIII reflex, a process closely related to visceral sensitivity, was also studied. R esults: During isobaric distensions, the discomfort threshold was sign ificantly higher in subjects on fedotozine than in those on placebo (1 4.4+/-0.92 vs. 12.0+/-1.13 mmHg; P = 0.04). Compared to placebo, fedot ozine did not modify gastric compliance and somatic sensitivity. Fedot ozine also reduced the inhibition of the RIII reflex induced by gastri c distension. Conclusion: Fedotozine decreases gastric sensitivity to distension by exerting specific action on gastric afferent pathways.