Preliminary evidence for the involvement of the putative 5-HT 4 receptor in zacopride- and copper sulphate-induced vomiting in the ferret

Abstract

Previous studies of the mechanism of zacopridc-induced emesis in ferrets have concluded that it is mediated predominantly by an antagonist effect on 5-HT 3 receptors although the possibility of a contribution from an agonist effect at 5-HT 4 receptors was not excluded. This study shows that zacopride (200 μg/kg p.o.)-induccd emesis can be blocked by a ‘high dose’ (1000 μg/kg) of ICS205930 but not by a low dose (100 μg/kg) or by ‘high doses’ (1000 μg/kg) of another more selective 5-HT 3 receptor antagonist granisetron. As ICS205930, at high doses, is reported to be a 5-HT 4 receptor antagonist it appears likely that activation of 5HT 4-reccptors contributes to emesis induced by zacopride. ‘High’ doses of ICS205930, but not granisetron or ondansetron, can also block the vagally mediated emesis induced by oral CuSO 4 suggesting that 5-HT 4 receptors involved in emesis are closely associated with abdominal vagal afferents.