Methadone conformation and opioid activity.
The inactive methadone analog threo-5-methylmethadone has a solid-state conformation in which the nitrogen is antiperiplanar to the tertiary carbon C(4). Since threo-5-methylmethadone exhibits no opioid agonism either in vivo or in vitro, methadone analogs probably do not have this conformation when bound to an opioid receptor. The potent agonist (-)-erythro-5-methylmethadone has a solid-state conformation in which the nitrogen atom is rotated back toward the phenyl rings on the quarternary carbon, suggesting that this unusual conformation is the active one.
D008691:Methadone / Q000031:analogs & derivatives / Q000494:pharmacology*; D008968:Molecular Conformation; D011957:Receptors, Opioid / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011957:Receptors, Opioid; C008191:isomethadone; C034073:5-methylmethadone; D008691:Methadone