Allosteric modulators of the α4β2 subtype of neuronal nicotinic acetylcholine receptors

Biochem Pharmacol. 2011 Oct 15;82(8):952-8. doi: 10.1016/j.bcp.2011.04.020. Epub 2011 May 7.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Animals
  • Humans
  • Ion Channel Gating / drug effects
  • Ligands
  • Nicotinic Agonists / chemistry
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Antagonists / chemistry
  • Nicotinic Antagonists / pharmacology*
  • Protein Isoforms
  • Receptors, Nicotinic* / metabolism
  • Receptors, Nicotinic* / physiology

Substances

  • Ligands
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Protein Isoforms
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2