Antiemetic activity of butorphanol against cisplatin-induced emesis in ferrets and dogs.
The analgesic agent butorphanol was evaluated for its ability to block cisplatin-induced emesis in ferrets and dogs. In ferrets, butorphanol (0.15, 0.3, or 0.45 mg/kg; expressed in terms of the tartrate salt) administered sc 30 minutes prior to cisplatin (8 mg/kg iv) reduced the number of emetic episodes but did not eliminate them. When these doses of butorphanol were administered 30 minutes before and 30 and 90 minutes after cisplatin, they caused a dose-related reduction in the number of emetic episodes; there was complete protection at a dose of 0.45 mg/kg/injection. In dogs, butorphanol (0.185 or 0.37 mg/kg/injection, expressed in terms of the tartrate salt) was administered sc on the same multiple-dose schedule used in the ferrets; this caused a nearly complete elimination of the emetic response to cisplatin (3 mg/kg iv). Butorphanol caused some sedation in both species at effective antiemetic doses but had no effect on the antitumor activity of cisplatin against murine L1210 leukemia. Naloxone blocked the antiemetic effect of butorphanol in ferrets, indicating the involvement of opiate receptors. The results of these studies suggest that butorphanol may be useful clinically in mitigating the emetic effects of cisplatin.
D000818:Animals; D002077:Butorphanol / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005289:Ferrets; D008297:Male; D051379:Mice; D009019:Morphinans / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D013997:Time Factors; D014839:Vomiting / Q000188:drug therapy*
D009019:Morphinans; D009270:Naloxone; D002945:Cisplatin; D002077:Butorphanol