Abstract
Agonists of the a4b2 nicotinic acetylcholine receptors have been synthesised as potential drugs for treatment of a variety of diseases. In this review, the published nicotinic agonists are presented and, on the basis of the molecular structure, the compounds are divided into three compound classes, nicotinoids (structurally close to nicotine), bicyclic compounds (structurally close to epibatidine and anatoxin-a), and analogues of imidacloprid (structurally close to the insecticide imidacloprid). The structure-activity relationships are discussed within and in between the classes. On the basis of computational studies of ligands for the nicotinic acetylcholine receptors the structure-activity relationships are discussed and a possible binding mode suggested. The binding mode encompasses (A) an interaction between an anionic site in the receptor and the protonated nitrogen atom in the ligand, (B) a hydrogen bond between a hydrogen bond donor in the receptor and a hydrogen bond acceptor in the ligand, (C) an interaction between a pi-system (heteroaromatic ring, carbonyl bond) in the ligand and another pi-system or a positively charged amino acid residue in the binding site, (D) a pi-cation interaction between aromatic residues in the receptor binding site and the protonated nitrogen atom in the ligand, and (E) steric interactions of positive and negative character around the aliphatic and the heteroaromatic part of the ligand.
Keywords: Molecular Modelling, Nicotinic Acetylcholine Receptors, Nicotinoids, Epibatidine, Agonists, Imidacloprid, Alzheimers patients, Parkinsons disease, Haloperidol, Dopamine antagonist
Current Medicinal Chemistry
Title: Agonists at the a4b2 Nicotinic Acetylcholine Receptors Relationships and Molecular Modelling
Volume: 8 Issue: 6
Author(s): J. E. Tonder and P. H. Olesen
Affiliation:
Keywords: Molecular Modelling, Nicotinic Acetylcholine Receptors, Nicotinoids, Epibatidine, Agonists, Imidacloprid, Alzheimers patients, Parkinsons disease, Haloperidol, Dopamine antagonist
Abstract: Agonists of the a4b2 nicotinic acetylcholine receptors have been synthesised as potential drugs for treatment of a variety of diseases. In this review, the published nicotinic agonists are presented and, on the basis of the molecular structure, the compounds are divided into three compound classes, nicotinoids (structurally close to nicotine), bicyclic compounds (structurally close to epibatidine and anatoxin-a), and analogues of imidacloprid (structurally close to the insecticide imidacloprid). The structure-activity relationships are discussed within and in between the classes. On the basis of computational studies of ligands for the nicotinic acetylcholine receptors the structure-activity relationships are discussed and a possible binding mode suggested. The binding mode encompasses (A) an interaction between an anionic site in the receptor and the protonated nitrogen atom in the ligand, (B) a hydrogen bond between a hydrogen bond donor in the receptor and a hydrogen bond acceptor in the ligand, (C) an interaction between a pi-system (heteroaromatic ring, carbonyl bond) in the ligand and another pi-system or a positively charged amino acid residue in the binding site, (D) a pi-cation interaction between aromatic residues in the receptor binding site and the protonated nitrogen atom in the ligand, and (E) steric interactions of positive and negative character around the aliphatic and the heteroaromatic part of the ligand.
Export Options
About this article
Cite this article as:
Tonder E. J. and Olesen H. P., Agonists at the a4b2 Nicotinic Acetylcholine Receptors Relationships and Molecular Modelling, Current Medicinal Chemistry 2001; 8 (6) . https://dx.doi.org/10.2174/0929867013373165
DOI https://dx.doi.org/10.2174/0929867013373165 |
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
-
Psychopathological Behaviour and Cognition in Morbid Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Chromosome 17 in Fronto Temporal Lobak Degeneration (FTLD): From MAPT to Progranulin and Back
Current Alzheimer Research Autoimmune Fibrotic Adverse Reactions in One-Year Treatment with Cabergoline for Women with Prolactinoma
Endocrine, Metabolic & Immune Disorders - Drug Targets Life Under Stress: The Probiotic Stress Response and How it may be Manipulated
Current Pharmaceutical Design Meet Our Editorial Board Member
CNS & Neurological Disorders - Drug Targets Body Mass Index in Midlife and Risk of Alzheimer Disease and Vascular Dementia
Current Alzheimer Research Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model
Current Molecular Medicine Involvement of Immune Response in the Pathogenesis of Amyotrophic Lateral Sclerosis: A Therapeutic Opportunity?
CNS & Neurological Disorders - Drug Targets Platelets: Their Potential Contribution to the Generation of Beta-amyloid Plaques in Alzheimer’s Disease
Current Neurovascular Research Gas Chromatography-electron Capture Detection Method for Determination of Polyols in the Urine
Current Organic Chemistry Humanized Cobra Venom Factor: Experimental Therapeutics for Targeted Complement Activation and Complement Depletion
Current Pharmaceutical Design Role of Matrix Metalloproteinases in Animal Models of Ischemic Stroke
Current Vascular Pharmacology Recent Advances in the Discovery of Selective and Non-Selective 5-HT1D Receptor Ligands
Current Topics in Medicinal Chemistry Social Markers of Mild Cognitive Impairment: Proportion of Word Counts in Free Conversational Speech
Current Alzheimer Research Regulation of Corticostriatal Synaptic Plasticity by G Protein-Coupled Receptors
CNS & Neurological Disorders - Drug Targets Exploring Molecular Approaches in Amyotrophic Lateral Sclerosis: Drug Targets from Clinical and Pre-Clinical Findings
Current Molecular Pharmacology Classification of Acetylcholinesterase Inhibitors and Decoys by a Support Vector Machine
Combinatorial Chemistry & High Throughput Screening Takotsubo Cardiomyopathy
Current Pharmaceutical Design Antibody Targeting of TGF-β in Cancer Patients
Current Pharmaceutical Biotechnology Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions
Current Neuropharmacology