Synthesis of analogues of acetylmethadol and methadol as potential narcotic antagonists.
The N-allyl and N-(cyclopropylmethyl) analogues of (-)-alpha-acetylmethadol and (-)-alpha-methadol have been synthesized and evaluated for opiate agonist and opiate antagonist activity. Both acetylmethadol analogues possessed weak analgesic activity in vivo tests for narcotic analgesia; the N-allyl analogue partially antagonized morphine-induced tail-flick analgesia. All four compounds possessed only opiate agonist-like activity as determined by in vitro studies measuring inhibition of [3H]naloxone binding to opiate receptors.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D008691:Methadone / Q000031:analogs & derivatives*; D008692:Methadyl Acetate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D009294:Narcotics / Q000138:chemical synthesis; D011957:Receptors, Opioid / Q000187:drug effects
D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D008692:Methadyl Acetate; D008691:Methadone