Tricyclic pyridones as functionally selective human GABAA alpha 2/3 receptor-ion channel ligands

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1679-82. doi: 10.1016/j.bmcl.2004.01.057.

Abstract

A series of tricyclic pyridones has been evaluated as benzodiazepine site ligands with functional selectivity for the alpha(3) over the alpha(1) containing subtype of the human GABA(A) receptor ion channel. This investigation led to the identification of a high affinity, functionally selective, orally bioavailable benzodiazepine site ligand that demonstrated activity in rodent anxiolysis models and reduced sedation relative to diazepam.

MeSH terms

  • Humans
  • Ion Channel Gating / physiology
  • Ligands
  • Protein Binding
  • Protein Subunits / metabolism*
  • Pyridones / chemistry*
  • Pyridones / metabolism*
  • Receptors, GABA-A / metabolism*

Substances

  • GABRA2 protein, human
  • Ligands
  • Protein Subunits
  • Pyridones
  • Receptors, GABA-A