Analgesic activity and toxicity of oripavine and phi-dihydrothebaine in the mouse and rat.
The analgesic activity of oripavine and phi-dihydrothebaine (5, 6, 8, 14-tetrahydro-4-hydroxy-3, 6-dimethoxy-17-methylmorphinan) has been studied in the mouse and rat with the hot-plate technique after s.c. drug administration. Peak analgesic effects in the mouse and rat were observed 20 min following drug administration, and the effect lasted about 40 to 60 min. Median analgesic (AD50) and lethal (LD50) doses and 95% confidence limits are presented. Oripavine and phi-dihydrothebaine appear to have analgesic potency of the same order as morphine in these species but have low therapeutic indexes because of severe toxicity. Toxic signs of oripavine and phi-dihydrothebaine in both species were clonic-tonic convulsions followed by death. The toxicity of oripavine, phi-dihydrothebaine and morphine in the mouse did not appear to be antagonized by pretreatment with 1 mg/kg of naloxone given 10 min prior to the test drug. toxicity does not appear to be mediated at the opiate receptor; however, oripavine did show some cross tolerance with morphine, but did not appear to suppress morphine abstinence in the mouse and rat.
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013797:Thebaine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000701:Analgesics, Opioid; D013797:Thebaine; D009270:Naloxone; C005283:oripavine; C033755:phi-dihydrothebaine; D009020:Morphine