Abstract
Enantiomers of erythro-5-methylmethadone (3) were synthesized from optical antipodes of erythro-3-(dimethylamino)-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 μ opioid receptors. On the other hand, (+)-3 and the more potent enantiomers of methadone, (−)-1, and isomethadone, (−)-2, appear to have less μ-receptor selectivity and interact with a greater fraction of δ 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 μ and δ receptors have different conformational requirements. The possibility of different modes of interaction with a single opioid receptor population also is discussed.
Original language | English (US) |
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Pages (from-to) | 684-688 |
Number of pages | 5 |
Journal | Journal of medicinal chemistry |
Volume | 25 |
Issue number | 6 |
DOIs | |
State | Published - Jan 1 1982 |