Abstract
Our investigation of bivalent ligands at mu, delta, and kappa opioid receptors is focused on the preparation of ligands containing kappa agonist and mu agonist/antagonist pharmacophores at one end joined by a chain containing the mu antagonist pharmacophores (naltrexone, naloxone, or nalbuphine) at the other end. These ligands were evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors and their relative efficacy in the [35S]GTPgammaS assay.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
-
Animals
-
CHO Cells
-
Cricetinae
-
Cricetulus
-
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
-
Humans
-
Ligands
-
Morphinans / chemical synthesis*
-
Morphinans / chemistry
-
Morphinans / pharmacology
-
Nalbuphine / analogs & derivatives*
-
Nalbuphine / chemical synthesis
-
Nalbuphine / pharmacology
-
Naloxone / analogs & derivatives*
-
Naloxone / chemical synthesis
-
Naloxone / pharmacology
-
Naltrexone / analogs & derivatives*
-
Naltrexone / chemical synthesis
-
Naltrexone / pharmacology
-
Radioligand Assay
-
Receptors, Opioid, delta / agonists
-
Receptors, Opioid, delta / antagonists & inhibitors
-
Receptors, Opioid, delta / drug effects*
-
Receptors, Opioid, kappa / agonists
-
Receptors, Opioid, kappa / antagonists & inhibitors
-
Receptors, Opioid, kappa / drug effects*
-
Receptors, Opioid, mu / agonists
-
Receptors, Opioid, mu / antagonists & inhibitors
-
Receptors, Opioid, mu / drug effects*
-
Structure-Activity Relationship
Substances
-
Ligands
-
Morphinans
-
Receptors, Opioid, delta
-
Receptors, Opioid, kappa
-
Receptors, Opioid, mu
-
butorphan
-
Naloxone
-
Guanosine 5'-O-(3-Thiotriphosphate)
-
Naltrexone
-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
-
Nalbuphine