Abstract
To characterize delta- and kappa-opioid receptor phenotypes, bivalent ligands (KDAN series) containing delta-antagonist (naltrindole) and kappa(1)-agonist (ICI-199,441) pharmacophores were synthesized and evaluated by the intrathecal route using the mouse tail-flick assay and binding studies. The data have suggested that KDAN-18 (2) bridges phenotypic delta(2)- and kappa(1)-receptors. A conceptual model is presented to explain the organizational differences between the opioid receptors that give rise to the phenotypes (delta(1), delta(2), kappa(1), kappa(2)).
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Allosteric Regulation
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology
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Animals
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Binding, Competitive
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Cell Line
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Humans
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Injections, Spinal
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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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Phenotype
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Pyrrolidines / chemistry
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Radioligand Assay
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Receptors, Opioid, delta / antagonists & inhibitors*
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Receptors, Opioid, kappa / agonists*
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Structure-Activity Relationship
Substances
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Amides
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KDAN 18
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Ligands
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Pyrrolidines
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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ICI 199441
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Naltrexone
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naltrindole