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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Cardiovascular Protective Effects of Chrysin: A Narrative Review on Experimental Researches
Cardiovascular & Hematological Agents in Medicinal Chemistry Targeting Nitrosative Stress for Neurovascular Protection: New Implications in Brain Diseases
Current Drug Targets Adipose Tissue as a Target of HIV-1 Antiretroviral Drugs. Potential Consequences on Metabolic Regulations
Current Pharmaceutical Design Isolated Anosmia as a Presentation of COVID-19: An Experience in a Referral Hospital
Infectious Disorders - Drug Targets Genomics and Pharmacogenomics of Salt-sensitive Hypertension
Current Hypertension Reviews Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise
Current Pharmaceutical Design Current Therapeutic Alternatives and New Perspectives in Glioblastoma Multiforme
Current Medicinal Chemistry Cognitive Decline as a Consequence of Essential Hypertension
Current Pharmaceutical Design Azithromycin and Dexamethasone Loaded β-Glucan Films for the Treatment of Blepharitis
Drug Delivery Letters Nitric Oxide-Mediated Endothelial Dysfunction - Is there Need to Treat?
Current Vascular Pharmacology Elevated Plasma Level of D-dimer Predicts the High Risk of Early Cognitive Impairment in Type 2 Diabetic Patients as Carotid Artery Plaques become Vulnerable or Get Aggravated
Current Alzheimer Research Obstructive Sleep Apnea and Hypertension: A Bidirectional Causal Relation
Current Respiratory Medicine Reviews GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons
Current Hypertension Reviews Sympathetic Overactivity in Hypertension and Cardiovascular Disease
Current Vascular Pharmacology Edaravone (3-Methyl-1-Phenyl-2-Pyrazolin-5-one), A Novel Free Radical Scavenger, for Treatment of Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Enhancement of Dissolution Rate of Furosemide Using a Solid Dispersion with D-Glucosamine HCl
Current Pharmaceutical Analysis A Dual Activity of ROS and Oxidative Stress on Adult Neurogenesis and Alzheimers Disease
Central Nervous System Agents in Medicinal Chemistry Genetically Modified Endothelial Progenitor Cells in the Therapy of Cardiovascular Disease and Pulmonary Hypertension
Current Vascular Pharmacology Gender Differences in Metabolic Syndrome – A Key Research Issue
Endocrine, Metabolic & Immune Disorders - Drug Targets Actinomycetes as a Paramount Source of Biologically Important Enzyme Inhibitors – “A Boon to Mankind”
Current Bioactive Compounds