Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes

Nat Rev Drug Discov. 2011 Jul 29;10(9):685-97. doi: 10.1038/nrd3502.


GABA(A) (γ-aminobutyric acid, type A) receptors are a family of ligand-gated ion channels that are essential for the regulation of central nervous system function. Benzodiazepines - which non-selectively target GABA(A) receptors containing the α1, α2, α3 or α5 subunits - have been in clinical use for decades and are still among the most widely prescribed drugs for the treatment of insomnia and anxiety disorders. However, their use is limited by side effects and the risk of drug dependence. In the past decade, the identification of separable key functions of GABA(A) receptor subtypes suggests that receptor subtype-selective compounds could overcome the limitations of classical benzodiazepines; furthermore, they might be valuable for novel indications such as chronic pain, depression, schizophrenia, cognitive enhancement and stroke.

Publication types

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

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Anxiety Disorders / drug therapy
  • Benzodiazepines / pharmacology*
  • Depressive Disorder / drug therapy
  • GABA Modulators / pharmacology
  • GABA Modulators / therapeutic use*
  • Humans
  • Hypnotics and Sedatives / pharmacology
  • Mutation / genetics
  • Mutation / physiology
  • Nootropic Agents / pharmacology
  • Receptors, GABA-A / classification
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / genetics
  • Schizophrenia / drug therapy
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Stroke / drug therapy
  • Substance-Related Disorders


  • Analgesics
  • GABA Modulators
  • Hypnotics and Sedatives
  • Nootropic Agents
  • Receptors, GABA-A
  • Benzodiazepines