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.
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.
Neumeyer
J L
JL
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. neumeyer@mclean.harvard.edu
Gu
X H
XH
van Vliet
L A
LA
DeNunzio
N J
NJ
Rusovici
D E
DE
Cohen
D J
DJ
Negus
S S
SS
Mello
N K
NK
Bidlack
J M
JM
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
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