Orientation of the oxygen atom at C-6 as a determinant of agonistic activity in the oxymorphone series.
The kinetics of various oxymorphones, their 6-methylene analogs and the 6-hydroxy-epimers corresponding to naloxone and naltrexone have been studied in the longitudinal muscle strip of the guinea-pig ileum. Substitution of the oxygen at C-6 by amethylene group slightly increased antagonistic activity of the resulting structures, without significantly influencing agonistic activity relative to the parent compound. The alpha-orientation of the hydroxy group at C-6 enhanced the agonistic property of both naloxone and naltrexone. The beta-compounds, however, were pure antagonists, with potencies similar to those of the parent keto structures.
D000818:Animals; D006168:Guinea Pigs; D004091:Hydromorphone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives; D009271:Naltrexone / Q000031:analogs & derivatives; D009292:Narcotic Antagonists; D010100:Oxygen; D010111:Oxymorphone; D013329:Structure-Activity Relationship
D009292:Narcotic Antagonists; D009270:Naloxone; D009271:Naltrexone; D010111:Oxymorphone; D004091:Hydromorphone; D010100:Oxygen