1982/06/01 by Philip S. Portoghese, Jacques H. Poupaert, Dennis L. Larson +5 · 1 citation
Agricultural and Biological Sciences · Chemistry · #Analytical Chemistry and Chromatography #Analytical Methods in Pharmaceuticals #Pharmacological Effects and Assays
paper · doi:10.1021/jm00348a015
openalex publication_date 1982/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Enantiomers of erythro-5-methylmethadone (3) were synthesized from optical antipodes of erythro-3-(dimethyl-amino)-2-butanol. X-ray crystallographic analysis of (-)-3 perchlorate revealed that it possesses the 5S,6S absolute configuration. It was found that (-)-3 is substantially more potent than its enantiomer (+)-3 as an opioid agonist in vivo and in vitro. In vitro tests (guinea pig ileal longitudinal muscle and mouse vas deferens preparations) suggest that (-)-3 mediates its effect chiefly through mu opioid receptors. On the other hand, (+)-3 and the more potent enantiomers of methadone, (-)-1, and isomethadone, (-)-2, appear to have less mu-receptor selectivity and interact with a greater fraction of delta receptors than does (-)-3. The fact that the solid-state conformation of (-)-3 differs from that of (-)-1 and (-)-2, which show great similarity in conformational features, suggests that mu and delta receptors have different conformational requirements. The possibility of different modes of interaction with a single opioid receptor population also is discussed.