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
-
Pharmacokinetic Modeling of Caco-2 Cell Permeability Using Genetic Programming (GP) Method
Letters in Drug Design & Discovery CuFe<sub>2</sub>O<sub>4</sub> Nanoparticle Mediated Method for the Synthesis of 5-Substituted 1H-Tetrazoles from (E)-Aldoximes
Letters in Organic Chemistry Heart Failure in Sub-Saharan Africa
Current Cardiology Reviews Platelet Function and Signaling in Diabetes Mellitus
Current Vascular Pharmacology Pharmacological and Lifestyle Factors Modulating Serum Paraoxonase-1 Activity
Mini-Reviews in Medicinal Chemistry Chloride Channels − New Targets for the Prevention of Stroke
Current Vascular Pharmacology Current Management of Peripheral Vascular Disease: Where is the Evidence?
Cardiovascular & Hematological Agents in Medicinal Chemistry Role of Azoles in Cancer Prevention and Treatment: Present and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Nature and Nurture in the Early-Life Origins of Metabolic Syndrome
Current Pharmaceutical Biotechnology Mutations of mtDNA in some Vascular and Metabolic Diseases
Current Pharmaceutical Design Artery of Percheron Infarction: A Characteristic Pattern of Ischemia and Variable Clinical Presentation: A Literature Review
Current Medical Imaging Synthesis of 3-(2, 8, 9-trioxa-5-aza-1-germatricyclo [3.3.3.0] Undecane-1- yl)-3-(4-hydroxyl-3-methoxyphenyl)-propionic Acid and its Inhibitory Effect on the Cervical Tumor U14 in vitro and in vivo
Medicinal Chemistry Editorial [Hot topic: Phosphodiesterase-5 Inhibitors and their Use in the Treatment of Urological Conditions (Executive Editor: Perimenis Petros)]
Current Pharmaceutical Design Syntheses, Transformations and Pharmaceutical Applications of Kynurenic Acid Derivatives
Current Medicinal Chemistry Pharmacological and Surgical Therapy for Primary Postpartum Hemorrhage
Current Pharmaceutical Design Imidazole: An Essential Edifice for the Identification of New Lead Compounds and Drug Development
Mini-Reviews in Medicinal Chemistry Vascular Biomarkers in Asthma and COPD
Current Topics in Medicinal Chemistry Salt: A Review of its Role in Food Science and Public Health
Current Nutrition & Food Science Pharmacological Applications of Antioxidants: Lights and Shadows
Current Drug Targets Blood Pressure and the Risk of Dementia: A Dose-Response Meta-Analysis of Prospective Studies
Current Neurovascular Research