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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Chemical Society
2014
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/37816/ http://irep.iium.edu.my/37816/1/Irna_Elina_%28Journal_of_Medicinal_Chemistry%29.pdf |
| _version_ | 1848781478581764096 |
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| 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 |
| building | IIUM Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T15:50:12Z |
| format | Article |
| id | iium-37816 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T15:50:12Z |
| publishDate | 2014 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| 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 |
| 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 |
| title | 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_short | 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 |
| topic | QD Chemistry RS Pharmacy and materia medica |
| 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 |