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-hydroxytryptamine (5-HT3)-receptor antagonist, delivered via intravenous and intraluminal routes, on the sensitivity of mesenteric afferent fibres supplying the proximal jejunum. Waveform analysis was performed to extract 5-HT sensitive single units from electrophysiological recordings of whole afferent nerve discharge. Dose effects of intravenous cilansetron (0.2-20 microg/kg) on the afferent response to 5-HT (10 microg) were examined to determine the threshold dose of cilansetron (2 microg/kg). This dose applied intraluminally to the region of jejunum innervated by the afferents, resulted in a greater degree of antagonism 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 afferent terminals.
Hillsley
K
K
Department of Biomedical Science, University of Sheffield, UK.
Eeckhout
C
C
Grundy
D
D
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D002227:Carbazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007275:Injections, Intravenous; D007583:Jejunum / Q000294:innervation*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*
D002227:Carbazoles; D011725:Pyridines; D012702:Serotonin Antagonists; C084473:cilansetron; D012701:Serotonin