Abstract
A structurally novel opioid kappa receptor selective ligand has been identified. This compound, (3R)-7-hydroxy-N-((1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic, 10) demonstrated high affinity for the kappa receptor in the binding assay (kappa K(i) = 0.3 nM) and highly potent and selective kappa antagonism in the [(35)S]GTP-gamma-S assay using cloned opioid receptors (kappa K(i) = 0.006 nM, mu/kappa ratio = 570, delta/kappa ratio > 16600).
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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Binding, Competitive
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Brain / metabolism
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Cloning, Molecular
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Guinea Pigs
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Humans
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In Vitro Techniques
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / metabolism
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Isoquinolines / pharmacology
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Narcotic Antagonists / chemical synthesis*
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Narcotic Antagonists / chemistry
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Narcotic Antagonists / metabolism
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Narcotic Antagonists / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / metabolism
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Piperidines / pharmacology
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Radioligand Assay
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Rats
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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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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / metabolism
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Structure-Activity Relationship
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Tetrahydroisoquinolines*
Substances
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7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide
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Isoquinolines
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Narcotic Antagonists
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Piperidines
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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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Tetrahydroisoquinolines