| Autor: |
Portoghese PS, Poupaert JH, Larson DL, Groutas WC, Meitzner GD, Swenson DC, Smith GD, Duax WL |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1982 Jun; Vol. 25 (6), pp. 684-8. |
| DOI: |
10.1021/jm00348a015 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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