Abstract
In view of recent pharmacological studies suggesting the existence of delta-kappa opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing kappa and delta antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal delta-kappa receptor heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The selectivity profile of KDN-21 and the apparent absence of coupled delta(1)-kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line
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Humans
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Ligands
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Mice
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Naltrexone / analogs & derivatives*
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Naltrexone / chemical synthesis*
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Naltrexone / chemistry
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Naltrexone / pharmacology
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Phenotype
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Receptors, Opioid, delta / antagonists & inhibitors*
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / antagonists & inhibitors*
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Receptors, Opioid, kappa / metabolism
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Structure-Activity Relationship
Substances
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KDN 21
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Ligands
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Oligopeptides
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Naltrexone
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naltrindole