Cilansetron acts at its site of absorption to antagonize the sensitivity of mesenteric afferent fibres to 5-hydroxytryptamine in the rat jejunum

The present study compares the efficacy of cilansetron, a 5-hydroxytryptami ne (5-HT3)-receptor antagonist, delivered via intravenous and intraluminal routes, on the sensitivity of mesenteric afferent fibres supplying the prox imal jejunum. Waveform analysis was performed to extract 5-HT sensitive sin gle units from electrophysiological recordings of whole afferent nerve disc harge. Dose effects of intravenous cilansetron (0.2-20 mu g/kg) on the affe rent response to 5-HT(10 mu g) were examined to determine the threshold dos e of cilansetron (2 mu g/kg). This dose applied intraluminally to the regio n of jejunum innervated by the afferents, resulted in a greater degree of a ntagonism of the 5-HT response than intravenous administration (47.8 +/- 7. 9 vs. 76.9 +/- 4.7%, P = 0.008). We concluded that cilansetron is active at its site of absorption to antagonize 5-HT3 receptors on vagal mucosal affe rent terminals. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.