Premium
Allosteric modifiers of neuronal nicotinic acetylcholine receptors: New methods, new opportunities
Author(s) -
Moaddel Ruin,
Jozwiak Krzysztof,
Wainer Irving W.
Publication year - 2007
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20091
Subject(s) - pharmacophore , nicotinic agonist , allosteric regulation , acetylcholine receptor , drug discovery , drug , computational biology , pharmacology , nicotinic acetylcholine receptor , chemistry , receptor , neuroscience , biology , biochemistry
Allosteric, non‐competitive inhibitors (NCIs) of neuronal nicotinic acetylcholine receptors (nAChRs) have been shown to produce a wide variety of clinically relevant responses. Many of the observed effects are desired as the nAChR is the therapeutic target, while others are undesired consequences due to off‐target binding at the nAChR. Thus, the determination of whether or not a lead drug candidate is an NCI should play an important role in drug discovery programs. However, the current experimental techniques used to identify NCIs are challenging, expensive, and time consuming. This review focuses on an alternative approach to the investigation of interactions between test compounds and nAChRs based upon liquid chromatographic stationary phases containing cellular fragments from cell lines expressing nAChRs. The development and validation of these phases as well as their use in drug discovery and pharmacophore modeling are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 723–753, 2007