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.
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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 |
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