Discovery of non-zwitterionic GABA(A) receptor full agonists and a superagonist

Bioorg Med Chem Lett. 2002 Aug 5;12(15):1985-8. doi: 10.1016/s0960-894x(02)00299-8.

Abstract

Numerous previous studies of GABA(A) receptor ligands have suggested that GABA(A) receptor agonists must be zwitterionic and feature an intercharge separation similar to that of GABA (approx. 4.7-6A). In this communication we demonstrate that appropriately functionalized GABA amides are partial, full, or superagonists, despite their non-zwitterionic structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / metabolism
  • Amides / pharmacology*
  • Animals
  • Binding, Competitive
  • Chlorides / metabolism
  • Dimerization
  • Dose-Response Relationship, Drug
  • GABA-A Receptor Agonists*
  • Ligands
  • Mice
  • Protein Binding
  • Receptors, GABA-A / metabolism
  • Structure-Activity Relationship
  • Synaptosomes / drug effects
  • Synaptosomes / physiology
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amides
  • Chlorides
  • GABA-A Receptor Agonists
  • Ligands
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid