title: Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan.
abstract: A series of new N-substituted derivatives of morphinan was synthesized and their binding affinity for the three opioid receptors (mu, delta, and kappa) was determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-iodoprop-(2E)-enyl) (MCL-118) substituents on the binding affinities for the mu and kappa opioid receptors was observed. All of these novel derivatives showed a preference for the mu and kappa versus delta binding.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. neumeyer@mclean.harvard.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Neumeyer
authors.forename: X H
authors.initials: XH
authors.lastname: Gu
authors.forename: L A
authors.initials: LA
authors.lastname: van Vliet
authors.forename: N J
authors.initials: NJ
authors.lastname: DeNunzio
authors.forename: D E
authors.initials: DE
authors.lastname: Rusovici
authors.forename: D J
authors.initials: DJ
authors.lastname: Cohen
authors.forename: S S
authors.initials: SS
authors.lastname: Negus
authors.forename: N K
authors.initials: NK
authors.lastname: Mello
authors.forename: J M
authors.initials: JM
authors.lastname: Bidlack
mesh_terms: D019970:Cocaine-Related Disorders / Q000188:drug therapy; D004338:Drug Combinations; D006801:Humans; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors
chemical_list: D004338:Drug Combinations; D009019:Morphinans; C440388:N-(3-iodoprop-(2)-enyl); C440369:N-propargyl; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu