Enhancement of GABAergic Activity: Neuropharmacological Effects of Benzodiazepines and Therapeutic Use in Anesthesiology

GABA is the major inhibitory neurotransmitter in the central nervous system (CNS). The type A GABA receptor (GABA_AR) system is the primary pharmacological target for many drugs used in clinical anesthesia. The α1, β2, and γ2 subunit-containing GABA_ARs located in the various parts of CNS are thought to be involved in versatile effects caused by inhaled anesthetics and classic benzodiazepines (BZD), both of which are widely used in clinical anesthesiology. During the past decade, the emergence of tonic inhibitory conductance in extrasynaptic GABA_ARs has coincided with evidence showing that these receptors are highly sensitive to the sedatives and hypnotics used in anesthesia. Anesthetic enhancement of tonic GABAergic inhibition seems to be preferentially increased in regions shown to be important in controlling memory, awareness, and sleep. This review focuses on the physiology of the GABA_ARs and the pharmacological properties of clinically used BZDs. Although classic BZDs are widely used in anesthesiological practice, there is a constant need for new drugs with more favorable pharmacokinetic and pharmacodynamic effects and fewer side effects. New hypnotics are currently developed, and promising results for one of these, the GABA_AR agonist remimazolam, have recently been published.