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

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

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 p...

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Main Authors: Kumar, Vinod, Ridzwan, Irna Elina, Grivas, Konstantinos, Lewis, John W, Clark, Mary J, Meurice, Claire, Jimenez-Gomez, Corina, Pogozheva, Irina, Mosberg, Henry, Traynor, John R, Husbands, Stephen M
Format: Article
Language:English
Published: American Chemical Society 2014
Subjects:
QD Chemistry
RS Pharmacy and materia medica
Online Access:http://irep.iium.edu.my/37816/
http://irep.iium.edu.my/37816/
http://irep.iium.edu.my/37816/
http://irep.iium.edu.my/37816/1/Irna_Elina_%28Journal_of_Medicinal_Chemistry%29.pdf
id iium-37816
recordtype eprints
spelling iium-378162018-06-20T00:46:34Z http://irep.iium.edu.my/37816/ Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity Kumar, Vinod Ridzwan, Irna Elina Grivas, Konstantinos Lewis, John W Clark, Mary J Meurice, Claire Jimenez-Gomez, Corina Pogozheva, Irina Mosberg, Henry Traynor, John R Husbands, Stephen M QD Chemistry RS Pharmacy and materia medica 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. American Chemical Society 2014-04-24 Article PeerReviewed application/pdf en http://irep.iium.edu.my/37816/1/Irna_Elina_%28Journal_of_Medicinal_Chemistry%29.pdf 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 http://pubs.acs.org/doi/abs/10.1021/jm401964y?journalCode=jmcmar 10.1021/jm401964y
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
topic QD Chemistry
RS Pharmacy and materia medica
spellingShingle QD Chemistry
RS Pharmacy and materia medica
Kumar, Vinod
Ridzwan, Irna Elina
Grivas, Konstantinos
Lewis, John W
Clark, Mary J
Meurice, Claire
Jimenez-Gomez, Corina
Pogozheva, Irina
Mosberg, Henry
Traynor, John R
Husbands, Stephen M
Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
description 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.
format Article
author Kumar, Vinod
Ridzwan, Irna Elina
Grivas, Konstantinos
Lewis, John W
Clark, Mary J
Meurice, Claire
Jimenez-Gomez, Corina
Pogozheva, Irina
Mosberg, Henry
Traynor, John R
Husbands, Stephen M
author_facet Kumar, Vinod
Ridzwan, Irna Elina
Grivas, Konstantinos
Lewis, John W
Clark, Mary J
Meurice, Claire
Jimenez-Gomez, Corina
Pogozheva, Irina
Mosberg, Henry
Traynor, John R
Husbands, Stephen M
author_sort Kumar, Vinod
title Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
title_short Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
title_full Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
title_fullStr Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
title_full_unstemmed Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
title_sort selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
publisher American Chemical Society
publishDate 2014
url http://irep.iium.edu.my/37816/
http://irep.iium.edu.my/37816/
http://irep.iium.edu.my/37816/
http://irep.iium.edu.my/37816/1/Irna_Elina_%28Journal_of_Medicinal_Chemistry%29.pdf
first_indexed 2023-09-18T20:54:13Z
last_indexed 2023-09-18T20:54:13Z
_version_ 1777410195815661568

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