Abstract
Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly their MOR activity. When administered systemically in mouse antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of relatively short duration whereas on central administration it had only a KOR-antagonist action of extremely long duration.
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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Cell Line
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Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
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Humans
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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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Pyrroles / chemistry*
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Radioligand Assay
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Receptors, Opioid, delta / drug effects
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Receptors, Opioid, kappa / antagonists & inhibitors*
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Receptors, Opioid, mu / agonists
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Structure-Activity Relationship
Substances
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17,17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-4,5-4',5'-diepoxy-6,6'-(benzylimino)(7,7'-bimorphinan)-3,3',14,14'-tetrol
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Analgesics
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Pyrroles
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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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norbinaltorphimine
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Guanosine 5'-O-(3-Thiotriphosphate)
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Naltrexone