Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The effects of different antiemetic agents on morphine-induced emesis in ferrets. 822 24

In the present studies we investigated the mechanism of action of prostaglandin E2 (1 mg/kg, i.p.) to induce emesis and defecation and/or tenesmus in the ferret. The emesis was antagonized significantly (P<0.05) by ondansetron (0.3 and 1 mg/kg, i.p.) and (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenlypiperidine hydrochloride (CP-99,994; 10 mg/kg, i.p.), but neither compound reduced defecations and/or tenesmus, with ondansetron (0.3 mg/kg) actually producing a slight increase (P<0.05). Droperidol (1 and 3 mg/kg), metoclopramide (0.3 and 3 mg/kg), domperidone (0.3 and 3 mg/kg), promethazine (0.3 and 3 mg/kg) and scopolamine (0.3 and 3 mg/kg) failed to reduce prostaglandin E2 induced emesis. However, droperidol (1 and 3 mg/kg) and scopolamine (0.3 and 3 mg/kg) reduced significantly the defecatory and/or tenesmus response (P<0.05). Bilateral abdominal vagotomy was ineffective to reduce emesis and defecations and/or tenesmus. The data suggests that 5-HT3 receptor and NK1 tachykinin receptor antagonists could be useful in the clinic to prevent emesis but not defecations induced by prostaglandin E2.
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PMID:Differential action of anti-emetic drugs on defecation and emesis induced by prostaglandin E2 in the ferret. 1684 11