The effects of different antiemetic agents on morphine-induced emesis in ferrets.
There is interest in the development of antiemetics other than dopamine receptor antagonists for the treatment of postoperative nausea and vomiting. A ferret model of morphine-induced emesis may have wider application in evaluating newer agents than the apomorphine dog model. This study describes the conditions for morphine-induced emesis in ferrets and evaluates five antiemetics that are prototypical of three different 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-shaped 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 isoflurane-O2 anesthesia. Ondansetron, a 5-HT3 receptor antagonist, reduced 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 mg/kg. Metoclopramide reduced vomiting episodes by 48% and 82% (3 and 10 mg/kg). Droperidol reduced vomiting episodes by 84% at 3 mg/kg. Naloxone 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 accompanied the reduction in total numbers of episodes. The significant reduction of morphine-induced emesis in the ferret by ondansetron, metoclopramide and droperidol is consistent with the reduction of postoperative emesis in man by these compounds when morphine was a component of the anesthetic regimen. These results suggested that the morphine ferret model may be useful for evaluating compounds having the potential for preventing and treating postoperative vomiting.
Wynn
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RL
Department of Pharmacology, School of Dentistry, University of Maryland at Baltimore 21201.
Essien
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Thut
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PD
D000758:Anesthesia; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D004329:Droperidol / Q000494:pharmacology; D005289:Ferrets; D017829:Granisetron / Q000494:pharmacology; D007275:Injections, Intravenous; D007530:Isoflurane; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D009020:Morphine; D009270:Naloxone / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D004329:Droperidol; D017829:Granisetron; D007530:Isoflurane; D008787:Metoclopramide; D009020:Morphine; D009270:Naloxone; D017294:Ondansetron