Journal article
Synthesis, x-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that .mu. and .delta. opioid receptors possess different stereochemical requirements
Journal of medicinal chemistry, Vol.25(6), pp.684-688
01/01/1982
DOI: 10.1021/jm00348a015
PMID: 6284938
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.
Details
- Title: Subtitle
- Synthesis, x-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that .mu. and .delta. opioid receptors possess different stereochemical requirements
- Creators
- P S Portoghese - Institute of Medicinal Plant DevelopmentJ H Poupaert - University of MinnesotaD L Larson - University of MinnesotaW C GroutasG D MeitznerD C SwensonG D SmithW L Duax
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.25(6), pp.684-688
- Publisher
- Amer Chemical Soc
- DOI
- 10.1021/jm00348a015
- PMID
- 6284938
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Number of pages
- 5
- Grant note
- GM-19684 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) RR-05716 / NCRR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR)
- Language
- English
- Date published
- 01/01/1982
- Academic Unit
- Chemistry
- Record Identifier
- 9984622045302771
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