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1.  Deconstruction of the α4β2 Nicotinic Acetylchloine (nACh) Receptor Positive Allosteric Modulator des-Formylflustrabromine (dFBr) 
Journal of medicinal chemistry  2011;54(20):7259-7267.
des -Formylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using 2-electrode voltage clamp techniques. Although the intact structure of 1 was found optimal, several deconstructed analogs retained activity. Neither the 6-bromo substituent nor the entire 2-position chain is required for activity. In particular, reduction of the olefinic side chain of 1, as seen with 6, not only resulted in retention of activity/potency but in enhanced selectivity for α4β2 versus α7 nACh receptors. Pharmacophoric features for the allosteric modulation of α4β2 nACh receptors by 1 were identified.
PMCID: PMC3200116  PMID: 21905680
2.  Allosteric modulators of the α4β2 subtype of Neuronal Nicotinic Acetylcholine Receptors 
Biochemical pharmacology  2011;82(8):952-958.
Nicotinic acetylcholine receptors are ligand-gated ion conducting transmembrane channels from the Cys-loop receptor super-family. The α4β2 subtype is the predominant heteromeric subtype of nicotinic receptors found in the brain. Allosteric modulators for α4β2 receptors interact at a site other than the orthosteric site where acetylcholine binds. Many compounds which act as allosteric modulators of the α4β2 receptors have been identified, with both positive and negative effects. Such allosteric modulators either increase or decrease the response induced by agonist on the α4β2 receptors. Here we discuss the concept of allosterism as it pertains to the α4β2 receptors and summarize the important features of allosteric modulators for this nicotinic receptor subtype.
PMCID: PMC3162104  PMID: 21596025
Nicotinic acetylcholine receptor; Allosteric modulation; Positive allosteric modulators; Negative allosteric modulators

Results 1-2 (2)