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.
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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 |
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