Oxymorphone-naltrexonazine, a mixed opiate agonist-antagonist.
Previous studies from our laboratories have reported the synthesis and pharmacological characteristics of a series of symmetrical opiate azines: naloxonazine, oxymorphonazine and naltrexonazine. We have now synthesized and characterized in binding assays and in vivo two asymmetrical azines: oxymorphone-naltrexonazine and oxymorphone-3-methoxynaltrexonazine. Oxymorphone-naltrexonazine, which theoretically could interact with the receptor as either an agonist or antagonist, displayed antagonist properties in vitro and in vivo. Oxymorphone-3-methoxynaltrexonazine, which theoretically could bind only as an agonist, possessed agonist properties in binding studies and was a potent analgesic in vivo.
D000698:Analgesia; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D004090:Dihydromorphine / Q000037:antagonists & inhibitors / Q000378:metabolism; D004723:Endorphins / Q000037:antagonists & inhibitors*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004091:Hydromorphone / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010111:Oxymorphone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology
D004723:Endorphins; D011957:Receptors, Opioid; C053394:oxymorphone-naltrexonazine; C053393:oxymorphone-3-methoxynaltrexonazine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D012964:Sodium; D010111:Oxymorphone; D004090:Dihydromorphine; D004091:Hydromorphone