The Role of GABA Receptor Agonists in Anesthesia and Sedation

Abstract

GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABA_A receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR. Many GABAAR agonists are used in anesthesia practice and sedation, including propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. There are advantages and disadvantages to each GABAAR agonist currently in clinical use. With increasing knowledge regarding the pharmacology of GABAAR agonists, however, newer sedative agents have been developed which employ 'soft pharmacology', a term used to describe the pharmacology of agents whereby their chemical configuration allows rapid metabolism into inactive metabolites after the desired therapeutic effect(s) has occurred. These newer 'soft' GABAAR agonists may well approach ideal sedative agents, as they can offer well-controlled, titratable activity and ultrashort action. This review provides an overview of the role that GABAAR agonists currently play in sedation and anesthesia, in addition to discussing the future role of novel GABAAR agonists in anesthesia and sedation.

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