Abstract
Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki=2nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki=21, 36 and 39nM).
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Camphanes
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Diterpenes, Clerodane / chemistry
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Diterpenes, Clerodane / isolation & purification
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Diterpenes, Clerodane / pharmacology*
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal / chemistry
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Drugs, Chinese Herbal / isolation & purification
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Drugs, Chinese Herbal / pharmacology*
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HEK293 Cells
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Humans
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Molecular Conformation
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Panax notoginseng
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Receptors, Opioid, kappa / agonists*
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Salvia / chemistry
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Salvia miltiorrhiza
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Structure-Activity Relationship
Substances
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Camphanes
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Diterpenes, Clerodane
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Drugs, Chinese Herbal
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Receptors, Opioid, kappa
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danshen dripping pill
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salvinorin A