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Allosteric Modulation of GABAA Receptor Function by General Anesthetics and Alcohols

  • Chapter
Pharmacology of GABA and Glycine Neurotransmission

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 150))

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Abstract

Since their introduction into clinical practice nearly 150 years ago, general anesthetics have become some of the most widely used and important therapeutic agents. Alcohol, specifically ethanol, is arguably the most important non-prescription drug in most Western countries. Despite over a century of research, the molecular mechanisms of action of general anesthetics and alcohols in the central nervous system (CNS) have remained elusive. Ligand-gated ion channels have emerged as promising molecular targets to mediate the CNS effects of both classes of drug. In this review, we aim to describe the actions of general anesthetics and alcohols on γ-aminobutyric acidA (GABAA) receptors. We will begin by summarizing the chemical classes of anesthetics. We will briefly examine contemporary experimental methodology and review the pharmacological criteria that can help define proteins that represent plausible molecular targets for general anesthetics and alcohols. We will then describe the actions of these agents on the GABAA receptors. The last decade has witnessed an explosion of such studies, and we will focus in particular on recent work which utilizes recombinant chimeric and mutated receptors to identify regions of the GABAA receptors that are important for the modulatory actions of general anesthetics and alcohols.

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  1. M. D. Krasowski
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  2. R. A. Harris
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  3. N. L. Harrison
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  1. Institute of Pharmacology and Toxicology, ETH and University of Zürich, Winterthurerstr. 190, CH-8057, Zürich, Switzerland

    Hanns Möhler

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Krasowski, M.D., Harris, R.A., Harrison, N.L. (2001). Allosteric Modulation of GABAA Receptor Function by General Anesthetics and Alcohols. In: Möhler, H. (eds) Pharmacology of GABA and Glycine Neurotransmission. Handbook of Experimental Pharmacology, vol 150. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56833-6_5

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