Pharmacological modulation of GABA_A receptors

Ligand-gated ion channels are integral membrane proteins that activate through a change in conformation upon transmitter binding and were identified as key players of brain function. GABA_A receptors are major inhibitory ligand-gated ion channels of this protein family. They are the target of many therapeutic compounds widely used in the clinic and continue to attract the attention of academic and pharmaceutical laboratories. Advances in the knowledge of the structure of GABA_A receptors at the molecular level with unprecedented resolution enabled the determination of the binding sites of many allosteric modulators revealing the nature of their interactions with the receptors. Herein, we review the latest findings on allosteric modulation of GABA_A receptors and their relevance to drug discovery.