Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand gated ion channels of broad distribution and structural heterogeneity. Their functional diversity demonstrated involvement in a variety of neuronal processes (e.g., sensory gating and cognitive function) and generated great interest in them as targets for therapeutic intervention in a number of neuropathological conditions and diseases. In order to control distinct nicotinic functions pharmacologically, it is important to design ligands that selectively interact with distinct receptor subtypes in such a way as to maximize the therapeutic effect and minimize the adverse effects. The α7 nAChR, a CNS subtype, has been the most intensively studied nAChR in recent years. Selective α7 nAChR agonists have been developed as potential candidates for the treatment of schizophrenia, cognitive disorders (including Alzheimers disease), and inflammation. Despite early concerns that the rapid desensitization property of the α7 nAChR would limit their therapeutic potential, several have already been advanced to clinical trials (e.g., PH-399733, Pfizer; MEM 3454, Memory Pharmaceuticals/Roche). Further development of allosteric modulators and pharmaceutically relevant antagonists might expand the therapeutic potential of compounds that target α7 nAChRs. In this review we briefly describe the structure and function of the α7 nAChR and its in vitro and in vivo pharmacology, discuss the clinical relevance of these efforts, and review the current progress in α7 ligand development.
Keywords: α7 neuronal nicotinic acetylcholine receptors (nAChRs), α7 selective nicotinic ligand, quinuclidine, allosteric modulator, radiolabeled imaging ligand
Current Medicinal Chemistry
Title: Selective α7 Nicotinic Acetylcholine Receptor Ligands
Volume: 13 Issue: 13
Author(s): Anatoly Mazurov, Terry Hauser and Craig H. Miller
Affiliation:
Keywords: α7 neuronal nicotinic acetylcholine receptors (nAChRs), α7 selective nicotinic ligand, quinuclidine, allosteric modulator, radiolabeled imaging ligand
Abstract: Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand gated ion channels of broad distribution and structural heterogeneity. Their functional diversity demonstrated involvement in a variety of neuronal processes (e.g., sensory gating and cognitive function) and generated great interest in them as targets for therapeutic intervention in a number of neuropathological conditions and diseases. In order to control distinct nicotinic functions pharmacologically, it is important to design ligands that selectively interact with distinct receptor subtypes in such a way as to maximize the therapeutic effect and minimize the adverse effects. The α7 nAChR, a CNS subtype, has been the most intensively studied nAChR in recent years. Selective α7 nAChR agonists have been developed as potential candidates for the treatment of schizophrenia, cognitive disorders (including Alzheimers disease), and inflammation. Despite early concerns that the rapid desensitization property of the α7 nAChR would limit their therapeutic potential, several have already been advanced to clinical trials (e.g., PH-399733, Pfizer; MEM 3454, Memory Pharmaceuticals/Roche). Further development of allosteric modulators and pharmaceutically relevant antagonists might expand the therapeutic potential of compounds that target α7 nAChRs. In this review we briefly describe the structure and function of the α7 nAChR and its in vitro and in vivo pharmacology, discuss the clinical relevance of these efforts, and review the current progress in α7 ligand development.
Export Options
About this article
Cite this article as:
Mazurov Anatoly, Hauser Terry and Miller H. Craig, Selective α7 Nicotinic Acetylcholine Receptor Ligands, Current Medicinal Chemistry 2006; 13 (13) . https://dx.doi.org/10.2174/092986706777442011
DOI https://dx.doi.org/10.2174/092986706777442011 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Prion Protein Peptides as Vaccines
Mini-Reviews in Medicinal Chemistry Elucidation of PLK1 Linked Biomarkers in Oesophageal Cancer Cell Lines: A Step Towards Novel Signaling Pathways by p53 and PLK1-Linked Functions Crosstalk
Protein & Peptide Letters Cross Talk between the Cardiovascular and Nervous Systems:Neurotrophic Effects of Vascular Endothelial Growth Factor (VEGF) and Angiogenic Effects of Nerve Growth Factor (NGF)-Implications in Drug Development
Current Pharmaceutical Design Radiopharmaceutical: Revolutionary Agents for Diagnosis
Current Radiopharmaceuticals Growth Restriction: Etiology, Maternal and Neonatal Outcome. A Review
Current Women`s Health Reviews Specialisation of the Tropomyosin Composition of Actin Filaments Provides New Potential Targets for Chemotherapy
Current Cancer Drug Targets Comparative Genomic Hybridization: A Valuable Tool for Genome-Scale Analysis of Rodent Cancer Models
Current Genomics A Glance Over the Cannabinoid Machinery to Design New Anti- Angiogenic Compounds
Mini-Reviews in Medicinal Chemistry Is a "Mitochondrial Psychiatry" in the Future? A Review
Current Psychiatry Reviews Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design Involvement of Uridine-Nucleotide-Stimulated P2Y Receptors in Neuronal Growth and Function
Central Nervous System Agents in Medicinal Chemistry Combination of Hypoxia and RNA-Interference Targeting VEGF Induces Apoptosis in Hepatoma Cells Via Autocrine Mechanisms
Current Pharmaceutical Biotechnology An Overview of Targeting Legumain for Inhibiting Cancers
Current Pharmaceutical Design An Integrative Systems Analysis of High-grade Glioma Cell Lines: TLRs, Wnt, BRCA1, Netrins, STXBP1 and MDH1 Provide Putative Molecular Targets for Therapeutic Intervention
Current Pharmacogenomics and Personalized Medicine Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology
Current Molecular Medicine A New Target for Diagnosis and Treatment of CNS Disorders: Agmatinergic System
Current Medicinal Chemistry Therapeutic Drug Monitoring of Busulfan in Transplantation
Current Pharmaceutical Design Hepatocyte Growth Factor Signaling in Cancer Metastasis
Current Signal Transduction Therapy Endothelial Dysfunction in Metabolic Diseases: Role of Oxidation and Possible Therapeutic Employment of N-acetylcysteine
Current Medicinal Chemistry