Synthesis, in vitro affinity, and efficacy of a bis 8-ethynyl-4H-imidazo[1,5a]- [1,4]benzodiazepine analogue, the first bivalent alpha5 subtype selective BzR/GABA(A) antagonist

J Med Chem. 2003 Dec 18;46(26):5567-70. doi: 10.1021/jm034164c.

Abstract

The synthesis and in vitro affinity of the alpha5beta3gamma2 (alpha5) subtype selective BzR/GABA(A) antagonist 7 is described. This ligand is selective for alpha5 subtypes in vitro and is a potent antagonist of the effects of diazepam only at alpha5beta3gamma2 subtypes (oocytes). Ligands such as 7 will be important in the determination of which physiological function(s) are subserved by this GABA(A) alpha5 subtype.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzodiazepinones / chemical synthesis*
  • Benzodiazepinones / chemistry
  • Benzodiazepinones / pharmacology
  • Cell Line
  • Chloride Channels / drug effects
  • Chloride Channels / physiology
  • Crystallography, X-Ray
  • GABA Antagonists / chemical synthesis*
  • GABA Antagonists / chemistry
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Antagonists*
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Ligands
  • Models, Molecular
  • Oocytes / drug effects
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Radioligand Assay
  • Receptors, GABA-A / physiology
  • Structure-Activity Relationship
  • Xenopus

Substances

  • 1,3-bis(8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine-3-carboxy)propyl diester
  • Benzodiazepinones
  • Chloride Channels
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Imidazoles
  • Ligands
  • Receptors, GABA-A