IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics

Though efficacious in managing chronic, severe pain, opioid analgesics are accompanied by significant adverse effects including constipation, tolerance, dependence, and respiratory depression. The life-threatening risks associated with µ opioid receptor agonist-based analgesics challenges their use...

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Main Authors: Kyle J. Rehrauer, Christopher W. Cunningham
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Pharmacological Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1043661823003225
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author Kyle J. Rehrauer
Christopher W. Cunningham
author_facet Kyle J. Rehrauer
Christopher W. Cunningham
author_sort Kyle J. Rehrauer
collection DOAJ
description Though efficacious in managing chronic, severe pain, opioid analgesics are accompanied by significant adverse effects including constipation, tolerance, dependence, and respiratory depression. The life-threatening risks associated with µ opioid receptor agonist-based analgesics challenges their use in clinic. A rational approach to combatting these adverse effects is to develop agents that incorporate activity at a second pharmacologic target in addition to µ opioid receptor activation. The promise of such bivalent or bifunctional ligands is the development of an analgesic with an improved side effect profile. In this review, we highlight ongoing efforts in the development of bivalent and bifunctional analgesics that combine µ agonism with efficacy at κ and δ opioid receptors, the nociceptin opioid peptide (NOP) receptor, σ receptors, and cannabinoid receptors. Several examples of bifunctional analgesics in preclinical and clinical development are highlighted, as are strategies being employed toward the rational design of novel agents.
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spelling doaj.art-18058b2dc17b40208b0dd4c0925174d62023-11-19T04:34:19ZengElsevierPharmacological Research1096-11862023-11-01197106966IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesicsKyle J. Rehrauer0Christopher W. Cunningham1Department of Pharmaceutical and Administrative Sciences, Concordia University Wisconsin School of Pharmacy, 12800 N. Lake Shore Drive, Mequon, WI 53092, USADepartment of Pharmaceutical and Administrative Sciences, Concordia University Wisconsin School of Pharmacy, 12800 N. Lake Shore Drive, Mequon, WI 53092, USA; CUW Center for Structure-Based Drug Discovery and Development, Concordia University Wisconsin School of Pharmacy, 12800 N. Lake Shore Drive, Mequon, WI 53092, USA; Corresponding author at: Department of Pharmaceutical and Administrative Sciences, Concordia University Wisconsin School of Pharmacy, 12800 N. Lake Shore Drive, Mequon, WI 53092, USA.Though efficacious in managing chronic, severe pain, opioid analgesics are accompanied by significant adverse effects including constipation, tolerance, dependence, and respiratory depression. The life-threatening risks associated with µ opioid receptor agonist-based analgesics challenges their use in clinic. A rational approach to combatting these adverse effects is to develop agents that incorporate activity at a second pharmacologic target in addition to µ opioid receptor activation. The promise of such bivalent or bifunctional ligands is the development of an analgesic with an improved side effect profile. In this review, we highlight ongoing efforts in the development of bivalent and bifunctional analgesics that combine µ agonism with efficacy at κ and δ opioid receptors, the nociceptin opioid peptide (NOP) receptor, σ receptors, and cannabinoid receptors. Several examples of bifunctional analgesics in preclinical and clinical development are highlighted, as are strategies being employed toward the rational design of novel agents.http://www.sciencedirect.com/science/article/pii/S1043661823003225AnalgesicsDrug designDrug discoveryOpioidBivalent ligandBifunctional ligand
spellingShingle Kyle J. Rehrauer
Christopher W. Cunningham
IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics
Pharmacological Research
Analgesics
Drug design
Drug discovery
Opioid
Bivalent ligand
Bifunctional ligand
title IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics
title_full IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics
title_fullStr IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics
title_full_unstemmed IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics
title_short IUPHAR Review - Bivalent and bifunctional opioid receptor ligands as novel analgesics
title_sort iuphar review bivalent and bifunctional opioid receptor ligands as novel analgesics
topic Analgesics
Drug design
Drug discovery
Opioid
Bivalent ligand
Bifunctional ligand
url http://www.sciencedirect.com/science/article/pii/S1043661823003225
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