The neuropharmacology of loperamide-induced emesis in the ferret: the role of the area postrema, vagus, opiate and 5-HT3 receptors

Abstract

Loperamide, an opiate receptor agonist, commonly used in the treatment of diarrhoea, reliably induced emesis in the ferret, when given subcutaneously. The response latency was short (less than 10 min) and the emesis lasted for approx 70 min. The dose-response curve for the emetic response was "bell-shaped" and all animals responded at 0.5 mg/kg but none at 5 mg/kg (s.c.). The response was unaffected by dopamine D2 receptor antagonism (domperidone 1.0 mg/kg, s.c.) or 5-HT3 receptor antagonism (granisetron or ondansetron 1.0 mg/kg, s.c.). The onset of the response was delayed for about 60 min by naloxone or naloxone methiodide (1.0 mg/kg, s.c.) and abolished by naloxanazine (1.0 mg/kg, s.c.), reported to be relatively selective for mu receptors. The results implicate mu receptors (possibly mu 1) in the induction of emesis by loperamide and provide some support for activation of opiate receptors also having anti-emetic effects, as suggested in previous studies. The emetic response to loperamide was unaffected by abdominal vagotomy but was abolished by ablation of the area postrema, indicating that loperamide-induced emesis may be used as a test for ablation of the area postrema in studies of the emetic mechanism in the ferret.