Preliminary evidence for the involvement of the putative 5-HT4 receptor in zacopride- and copper sulphate-induced vomiting in the ferret.
Previous studies of the mechanism of zacopride-induced emesis in ferrets have concluded that it is mediated predominantly by an antagonist effect on 5-HT3 receptors although the possibility of a contribution from an agonist effect at 5-HT4 receptors was not excluded. This study shows that zacopride (200 micrograms/kg p.o.)-induced emesis can be blocked by a 'high dose' (1000 micrograms/kg) of ICS205930 but not by a low dose (100 micrograms/kg) or by 'high doses' (1000 micrograms/kg) of another more selective 5-HT3 receptor antagonist granisetron. As ICS205930, at high doses, is reported to be a 5-HT4 receptor antagonist it appears likely that activation of 5HT4-receptors 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 CuSO4 suggesting that 5-HT4 receptors involved in emesis are closely associated with abdominal vagal afferents.
Bhandari
P
P
Department of Physiology, St. George's Hospital Medical School, London, U.K.
Andrews
P L
PL
D000704:Analysis of Variance; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003300:Copper / Q000494:pharmacology*; D019327:Copper Sulfate; D005260:Female; D005289:Ferrets; D017829:Granisetron; D007093:Imidazoles / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008139:Loperamide / Q000494:pharmacology; D008297:Male; D017294:Ondansetron; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced / Q000503:physiopathology*
D000932:Antiemetics; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003300:Copper; D019327:Copper Sulfate; D017829:Granisetron; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D008139:Loperamide; D017294:Ondansetron; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000077526:Tropisetron; C055971:zacopride