Frontiers in Medicinal Chemistry

Volume: 3

Indexed in: Scopus, EMBASE, Chemical Abstracts, EBSCO, Ulrich's Periodicals Directory.

Frontiers in Medicinal Chemistry is a book series devoted to the review of areas of important topical interest to medicinal chemists and others in allied disciplines. Frontiers in Medicinal Chemistry ...
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Design of Ligands for the Nicotinic Acetylcholine Receptors: The Quest for Selectivity

Pp. 195-247 (53)

William H. Bunnelle, Michael J. Dart and Michael R. Schrimpf


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.


Nicotine, epibatidine, acetylcholine, quinuclidine, nAChR, α4β2, α7, SAR


Abbott Laboratories Global Pharmaceutical Research and Development, Department R47W, AP9A-1, Abbott Park, Illinois 60064, USA.