Abstract
Bivalent ligands have been developed for a variety of G protein-coupled receptor targets, including opioid, dopamine, serotonin and muscarinic receptors. The most successful application of the bivalent ligand approach has been in the development of selective opioid antagonists, such as norbinaltorphimine. Several important principles have emerged from the study of norbinaltorphimine and related compounds, including the utility of bivalent ligands for targeting particular receptor classes and serving as a scaffold for specific interactions with unique amino acid residues that render receptor subtype selectivity. In recent years, several novel bivalent compounds were synthesized and characterized for activity at muscarinic receptors. The compounds display an interesting profile of high binding affinity, strong agonist potency and receptor subtype selectivity. Bivalent ligands represent an important starting point for the development of selective muscarinic agonists with potential utility in treating a variety of neurological disorders, including Alzheimers disease and schizophrenia. The bivalent ligand approach may be generally applicable to other G protein-coupled receptors.
Keywords: bivalent ligand, muscarinic receptor, opioid receptor, drug design, serotonin receptor
Current Pharmaceutical Design
Title: Bivalent Ligands for G Protein-Coupled Receptors
Volume: 10 Issue: 17
Author(s): William S. Messer, Jr.
Affiliation:
Keywords: bivalent ligand, muscarinic receptor, opioid receptor, drug design, serotonin receptor
Abstract: Bivalent ligands have been developed for a variety of G protein-coupled receptor targets, including opioid, dopamine, serotonin and muscarinic receptors. The most successful application of the bivalent ligand approach has been in the development of selective opioid antagonists, such as norbinaltorphimine. Several important principles have emerged from the study of norbinaltorphimine and related compounds, including the utility of bivalent ligands for targeting particular receptor classes and serving as a scaffold for specific interactions with unique amino acid residues that render receptor subtype selectivity. In recent years, several novel bivalent compounds were synthesized and characterized for activity at muscarinic receptors. The compounds display an interesting profile of high binding affinity, strong agonist potency and receptor subtype selectivity. Bivalent ligands represent an important starting point for the development of selective muscarinic agonists with potential utility in treating a variety of neurological disorders, including Alzheimers disease and schizophrenia. The bivalent ligand approach may be generally applicable to other G protein-coupled receptors.
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Cite this article as:
Messer, Jr. S. William, Bivalent Ligands for G Protein-Coupled Receptors, Current Pharmaceutical Design 2004; 10 (17) . https://dx.doi.org/10.2174/1381612043384213
DOI https://dx.doi.org/10.2174/1381612043384213 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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