Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity

Kumar, Vinod and Ridzwan, Irna Elina and Grivas, Konstantinos and Lewis, John W and Clark, Mary J and Meurice, Claire and Jimenez-Gomez, Corina and Pogozheva, Irina and Mosberg, Henry and Traynor, John R and Husbands, Stephen M (2014) Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity. Journal of Medicinal Chemistry, 57. pp. 4049-4057. ISSN 0022-2623

PDF - Published Version Restricted to Repository staff only Download (3MB) | Request a copy

Abstract

Emerging clinical and preclinical evidence suggests that a compound displaying high affinity for μ, κ, and δ opioid (MOP, KOP, and DOP) receptors and antagonist activity at each, coupled with moderate affinity and efficacy at nociceptin opioid peptide (NOP) receptors will have utility as a relapse prevention agent for multiple types of drug abuse. Members of the orvinol family of opioid ligands have the desired affinity profile but have typically displayed substantial efficacy at MOP and or KOP receptors. In this study it is shown that a phenyl ring analogue (1d) of buprenorphine displays the desired profile in vitro with high, nonselective affinity for the MOP, KOP, and DOP receptors coupled with moderate affinity for NOP receptors. In vivo, 1d lacked any opioid agonist activity and was an antagonist of both the MOP receptor agonist morphine and the KOP receptor agonist ethylketocyclazocine, confirming the desired opioid receptor profile in vivo.

Item Type:	Article (Journal)
Additional Information:	5628/37816
Uncontrolled Keywords:	Promiscuous Opioid Ligands
Subjects:	Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy
Depositing User:	Dr Irna Elina Ridzwan
Date Deposited:	21 Aug 2014 15:37
Last Modified:	20 Jun 2018 08:46
URI:	http://irep.iium.edu.my/id/eprint/37816

Actions (login required)

View Item