THE EFFECTS OF DIFFERENT ANTIEMETIC AGENTS ON MORPHINE-INDUCED EMESISIN FERRETS

There is interest in the development of antiemetics other than dopamin e receptor antagonists for the treatment of postoperative nausea and v omiting. A ferret model of morphine-induced emesis may have wider appl ication in evaluating newer agents than the apomorphine dog model. Thi s study describes the conditions' for morphine-induced emesis in ferre ts and evaluates five antiemetics that are prototypical of three diffe rent mechanisms. The average numbers of vomiting and retching episodes induced by morphine (0.1-2.5 mg/kg s.c.) were distributed as a bell-s haped curve. Maximum number of vomits occurred at 0.3 mg/kg (11.8 +/- 2.1 vomits; 45 +/- 12.5 retches). Antiemetics or vehicle were given i. v. 5 min prior to morphine while each ferret was maintained under isof lurane-O2 anesthesia. Ondansetron, a 5-HT3 receptor antagonist, reduce d vomiting episodes by 47% and 70% (3 and 10 mg/kg). Granisetron, a 5- HT3 receptor antagonist was inactive at doses of 0.1, 1.0 3.0 and 10 m g/kg. Metoclopramide reduced vomiting episodes by 48% and 82% (3 and 1 0 mg/kg). Droperidol reduced vomiting episodes by 84% at 3 mg/kg. Nalo xone reduced vomiting episodes by 91% and 43% at doses of 0.1 and 1.0 mg/kg. In most cases, prolonged latency times to the first episodes ac companied the reduction in total numbers of episodes. The significant reduction of morphine-induced emesis in the ferret by ondansetron, met oclopramide and droperidol is consistent with the reduction of postope rative emesis in man by these compounds when morphine was a component of the anesthetic regimen. These results suggested that the morphine f erret model may be useful for evaluating compounds having the potentia l for preventing and treating postoperative vomiting.