Abstract
The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while the TNTI derivatives (7) were potent DOR antagonists or low-efficacy DOR partial agonists without substantial selectivity. The TOMI derivatives (8) were DOR agonists with significant selectivity. In vivo the DOR antagonist activity of 7d was confirmed, but the predominant agonist effect of 8d was shown to be mu opioid receptor mediated.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / chemistry
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Analgesics / pharmacology
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Animals
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Binding, Competitive
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CHO Cells
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Cricetinae
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Cricetulus
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Ligands
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Morphinans / chemical synthesis*
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Morphinans / chemistry
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Morphinans / pharmacology
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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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Radioligand Assay
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, kappa / antagonists & inhibitors
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Receptors, Opioid, mu / agonists
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Receptors, Opioid, mu / antagonists & inhibitors
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Structure-Activity Relationship
Substances
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17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7-2',3'-pyrrolomorphinan
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Analgesics
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Indoles
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Ligands
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Morphinans
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Naltrexone