title: Pharmacological properties of bivalent ligands containing butorphan linked to nalbuphine, naltrexone, and naloxone at mu, delta, and kappa opioid receptors.
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.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Peng
authors.forename: Brian I
authors.initials: BI
authors.lastname: Knapp
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009266:Nalbuphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009270:Naloxone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D009019:Morphinans; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C520649:butorphan; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009266:Nalbuphine