Abstract
In the last decade, nicotinic acetylcholine receptors (nAChRs) have emerged as important targets for drug discovery. The therapeutic potential of nicotinic agonists depends substantially on the ability to selectively activate certain receptor subtypes that mediate beneficial effects. The design of such compounds has proceeded in spite of a general shortage of data pertaining to subtype selectivity. Medicinal chemistry efforts have been guided principally by binding affinities to the α4β2 and / or α7 subtypes, even though these are not predictive of agonist activity at either subtype. Nevertheless, a diverse family of nAChR ligands has been developed, and several analogs with promising therapeutic potential have now advanced to human clinical trials. This paper provides an overview of the structure-affinity relationships that continue to drive development of new nAChR ligands.
Keywords: Nicotine, epibatidine, acetylcholine, quinuclidine, nAChR, SAR
Current Topics in Medicinal Chemistry
Title: Design of Ligands for the Nicotinic Acetylcholine Receptors:The Quest for Selectivity
Volume: 4 Issue: 3
Author(s): W.H. Bunnelle, Manlio M.J. Dart and M.R. Schrimpf
Affiliation:
Keywords: Nicotine, epibatidine, acetylcholine, quinuclidine, nAChR, SAR
Abstract: In the last decade, nicotinic acetylcholine receptors (nAChRs) have emerged as important targets for drug discovery. The therapeutic potential of nicotinic agonists depends substantially on the ability to selectively activate certain receptor subtypes that mediate beneficial effects. The design of such compounds has proceeded in spite of a general shortage of data pertaining to subtype selectivity. Medicinal chemistry efforts have been guided principally by binding affinities to the α4β2 and / or α7 subtypes, even though these are not predictive of agonist activity at either subtype. Nevertheless, a diverse family of nAChR ligands has been developed, and several analogs with promising therapeutic potential have now advanced to human clinical trials. This paper provides an overview of the structure-affinity relationships that continue to drive development of new nAChR ligands.
Export Options
About this article
Cite this article as:
W.H. Bunnelle , M.J. Dart Manlio and M.R. Schrimpf , Design of Ligands for the Nicotinic Acetylcholine Receptors:The Quest for Selectivity, Current Topics in Medicinal Chemistry 2004; 4 (3) . https://dx.doi.org/10.2174/1568026043451438
DOI https://dx.doi.org/10.2174/1568026043451438 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Advances in the Development of Bradykinin Receptor Ligands
Current Topics in Medicinal Chemistry Biotechnological Approaches for the Treatment of Inflammatory Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cancer Drug Discovery Targeting Histone Methyltransferases: An Update
Current Medicinal Chemistry Stairway to Heaven or Hell? Perspectives and Limitations of Chagas Disease Chemotherapy
Current Topics in Medicinal Chemistry Optimal Sedation for the Ventilation of Critically Ill Patients
Current Respiratory Medicine Reviews Structure-Function Relationships of Phytochemicals in Control of Mosquito Vectors
Current Organic Chemistry Pharmacophore Identification and Quantitative Bioactivity Prediction Using the Electron-Conformational Method
Current Pharmaceutical Design The Fight against Human Viruses: How NMR Can Help?
Current Medicinal Chemistry Self-Medication with Antibiotics in Europe: A Case for Action
Current Drug Safety Factors Influencing Outcome of Patients Receiving Extracorporeal Membrane Oxygenation for Neonatal and Pediatric Respiratory Failure
Current Respiratory Medicine Reviews Screening Active Phytochemicals of Some Ayurvedic Medicinal Plants to Identify Potential Inhibitors against SARS-CoV-2 M<sup>pro</sup> by Computational Investigation
Letters in Drug Design & Discovery Progress in the Search for New Dopamine Transporter Inhibitors
Current Medicinal Chemistry Ligand-Receptor Communication and Drug Design
Current Protein & Peptide Science Antiviral Activity of Pyrimidine Containing Compounds: Patent Review
Mini-Reviews in Medicinal Chemistry An Overview of EEG Seizure Detection Units and Identifying their Complexity- A Review
Current Signal Transduction Therapy Inhibition of S-protein RBD and hACE2 Interaction for Control of SARSCoV- 2 Infection (COVID-19)
Mini-Reviews in Medicinal Chemistry Novel Coronavirus in India and Outbreaks Around World: A Statistical Analysis of Odisha, India and the World
Coronaviruses Inhibitors of the Mitochondrial Electron Transport Chain and de novo Pyrimidine Biosynthesis as Antimalarials: The Present Status
Current Medicinal Chemistry Gastrin: An Acid-Releasing, Proliferative and Immunomodulatory Peptide?
Mini-Reviews in Medicinal Chemistry Cancer Stem Cells and their Management in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery