5-HT3 receptor agonism may be responsible for the emetic effects of zacopride in the ferret.
The racemic 5-HT3 receptor antagonist, zacopride (10-100 micrograms kg-1, i.m.) evoked an emetic response in ferrets. This property appeared to reside totally in the S-enantiomer which also produced emesis over the same dose range. This emesis could be prevented by pretreatment with ondansetron (1 mg kg-1, i.m.) or by R-zacopride (100 micrograms kg-1, i.m.). In urethane-anaesthetized ferrets, S-zacopride (0.3 micrograms kg-1, i.v.) evoked a profound Bezold-Jarisch reflex which was blocked by both ondansetron (30 micrograms kg-1, i.v.) and by R-zacopride (100 micrograms kg-1, i.v.). These results suggest that, in the ferret, S-zacopride possesses 5-HT3 receptor agonist properties which may be responsible for the emetic effect. In contrast R-zacopride does not appear to possess 5-HT3 receptor agonist properties in this species.
Middlefell
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Department of Biomedical Research, Wyeth Research Ltd, Maidenhead, Berkshire, UK.
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D000758:Anesthesia; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004639:Emetics; D005260:Female; D005289:Ferrets; D007093:Imidazoles / Q000494:pharmacology; D017294:Ondansetron; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004639:Emetics; D007093:Imidazoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017294:Ondansetron; C055971:zacopride