Abstract
A series of naltrexone-derived pyridomorphinans possessing various substituents at the 5'-position on the pyridine ring were synthesized and evaluated for opioid receptor binding in rodent brain membranes and functional activity in smooth muscle preparations. While the introduction of aromatic 1-pyrrolyl group (6h) improved the delta affinity and delta antagonist potency of the parent compound (3), the introduction of guanidine group (6i) transformed it to a kappa selective ligand in opioid receptor binding and [35S]GTP-gamma-S functional assays.
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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Brain Chemistry / drug effects
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Guanidines / chemical synthesis
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Guanidines / pharmacology
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Guinea Pigs
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Ileum / drug effects
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In Vitro Techniques
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Indicators and Reagents
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Male
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Morphinans / chemical synthesis*
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Morphinans / pharmacology*
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / metabolism
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Naltrexone / analogs & derivatives*
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Naltrexone / chemical synthesis
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Naltrexone / pharmacology
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Narcotic Antagonists / chemical synthesis
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Narcotic Antagonists / pharmacology
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Pyridines / chemical synthesis
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Pyridines / pharmacology
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Rats
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Receptors, Opioid / drug effects
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Receptors, Opioid / metabolism*
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Receptors, Opioid, delta / antagonists & inhibitors
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Receptors, Opioid, delta / drug effects
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / antagonists & inhibitors
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Receptors, Opioid, kappa / drug effects
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / drug effects
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Receptors, Opioid, mu / metabolism
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Structure-Activity Relationship
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Vas Deferens / drug effects
Substances
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Guanidines
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Indicators and Reagents
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Morphinans
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Narcotic Antagonists
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Pyridines
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Receptors, Opioid
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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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Guanosine 5'-O-(3-Thiotriphosphate)
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Naltrexone