Abstract
Nicotinic acetylcholine receptors are ligand-gated transmembrane ion channels that are present at the neuromuscular junction and in different locations in the nervous system. The different subtypes of neuronal nicotinic acetylcholine receptors that are found in the brain are thought to be involved in many neurological processes such as pain, cognitive function and depression, as well as in the pathophysiology of numerous neurological diseases and conditions. While the neurotransmitter acetylcholine is an endogenous agonist for all nicotinic receptors subtypes, many drugs that act as agonists and antagonists have also been identified or developed for these receptors. In addition, a novel class of compounds described as allosteric modulators have also been identified or developed for nicotinic acetylcholine receptors. Allosteric modulators are ligands that bind to nicotinic receptors at sites other than the orthosteric site where acetylcholine binds. One such allosteric modulator is desformylflustrabromine. Five chemical analogs along with desformylflustrabromine act as positive allosteric modulator for nAChRs that contain the beta2 subunit in their pentameric structure. Here the discovery and development, medicinal chemistry and pharmacological actions of desformylflustrabromine have been discussed. Desformylflustrabromine and its chemical analogs have the potential to develop into clinically used drugs for neurological diseases and conditions where nicotinic acetylcholine receptors are involved.
Keywords: Allosteric modulation, Desformylflustrabromine, functional effects, nicotinic acetylcholine receptor, positive allosteric modulators.
Current Pharmaceutical Design
Title:Desformylflustrabromine: A Novel Positive Allosteric Modulator for beta2 Subunit Containing Nicotinic Receptor Sub-Types
Volume: 22 Issue: 14
Author(s): Anshul A. Pandya
Affiliation:
Keywords: Allosteric modulation, Desformylflustrabromine, functional effects, nicotinic acetylcholine receptor, positive allosteric modulators.
Abstract: Nicotinic acetylcholine receptors are ligand-gated transmembrane ion channels that are present at the neuromuscular junction and in different locations in the nervous system. The different subtypes of neuronal nicotinic acetylcholine receptors that are found in the brain are thought to be involved in many neurological processes such as pain, cognitive function and depression, as well as in the pathophysiology of numerous neurological diseases and conditions. While the neurotransmitter acetylcholine is an endogenous agonist for all nicotinic receptors subtypes, many drugs that act as agonists and antagonists have also been identified or developed for these receptors. In addition, a novel class of compounds described as allosteric modulators have also been identified or developed for nicotinic acetylcholine receptors. Allosteric modulators are ligands that bind to nicotinic receptors at sites other than the orthosteric site where acetylcholine binds. One such allosteric modulator is desformylflustrabromine. Five chemical analogs along with desformylflustrabromine act as positive allosteric modulator for nAChRs that contain the beta2 subunit in their pentameric structure. Here the discovery and development, medicinal chemistry and pharmacological actions of desformylflustrabromine have been discussed. Desformylflustrabromine and its chemical analogs have the potential to develop into clinically used drugs for neurological diseases and conditions where nicotinic acetylcholine receptors are involved.
Export Options
About this article
Cite this article as:
Pandya A. Anshul, Desformylflustrabromine: A Novel Positive Allosteric Modulator for beta2 Subunit Containing Nicotinic Receptor Sub-Types, Current Pharmaceutical Design 2016; 22 (14) . https://dx.doi.org/10.2174/1381612822666160127113159
DOI https://dx.doi.org/10.2174/1381612822666160127113159 |
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
-
Immunotherapy of Melanoma
Current Molecular Pharmacology T Cell Replicative Senescence in Human Aging
Current Pharmaceutical Design Improved Prediction of Protein Ligand-Binding Sites Using Random Forests
Protein & Peptide Letters The Role of the Nervous System in the Regulation of Liver Cytochrome P450
Current Drug Metabolism MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Current Immunology Reviews (Discontinued) Depression in Sleep Related Breathing Disorder
Current Respiratory Medicine Reviews Multipotent, Permeable Drug ASS234 Inhibits Aβ Aggregation, Possesses Antioxidant Properties and Protects from Aβ-induced Apoptosis In Vitro
Current Alzheimer Research NPY Y2 and Y4 Receptors Selective Ligands: Promising Anti-Obesity Drugs?
Current Topics in Medicinal Chemistry The Role of Berberine in the Multi-Target Treatment of Senile Dementia
Current Topics in Medicinal Chemistry Disrupted Functional Connectivity Related to Differential Degeneration of the Cingulum Bundle in Mild Cognitive Impairment Patients
Current Alzheimer Research In Silico Studies of (2E,5E)-2,5-bis(3-methoxy-4-hydroxy-benzylidene) Cyclopentanone on Proteins AChE and BChE Involved in Alzheimers disease and Ameliorative Effects on Paraquat Induced Oxidative Stress Markers in Drosophila melanogaster
Letters in Drug Design & Discovery Repositioning of DHFR Inhibitors
Current Topics in Medicinal Chemistry Various Techniques for Measuring Physiological Parameters Using WSN: Current State of the Art and Challenges
International Journal of Sensors, Wireless Communications and Control Is Educational Attainment Associated with Increased Risk of Mortality in People with Dementia? A Population-based Study
Current Alzheimer Research Applications of Chemical Shift Imaging for AD
Current Medical Imaging Author Index to Volume 1
Current Neurovascular Research Distinct Functions of cis and trans Phosphorylated Tau in Alzheimer's Disease and their Therapeutic Implications
Current Molecular Medicine Therapeutic Progress and Knowledge Basis on the Natriuretic Peptide System in Heart Failure
Current Topics in Medicinal Chemistry Endogenous Regulation of Neural Stem Cells in the Adult Mammalian Brain
Central Nervous System Agents in Medicinal Chemistry Drug Development of Small-Molecule Inhibitors of AD-Relevant Kinases as Novel Perspective Multitargeted Approach
Current Alzheimer Research