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Sleep-Wake Neurobiology and Pharmacology pp 279–304Cite as

GABA Receptors and the Pharmacology of Sleep

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 253))

Abstract

Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABAA receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at α2βγ2-type GABAA receptors. Drugs acting at more selective receptor types, for example, at receptors containing the α2 and/or α3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates αβδ-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABAA receptors, continue to be some of the most effective compounds to treat primary insomnia.

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Acknowledgements

The authors declare no financial conflict of interest. Work in the Franks and Wisden laboratory is funded by the Wellcome Trust (107839/Z/15/Z, N.P.F. and 107841/Z/15/Z, W.W).

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Authors and Affiliations

  1. Department Life Sciences, Imperial College London, London, SW7 2AZ, UK

    W. Wisden, X. Yu & N. P. Franks

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  1. W. Wisden
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  2. X. Yu
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  3. N. P. Franks
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Correspondence to W. Wisden .

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Editors and Affiliations

  1. Human Sleep Psychopharmacology Laboratory, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland

    Hans-Peter Landolt

  2. Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

    Derk-Jan Dijk

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Wisden, W., Yu, X., Franks, N.P. (2017). GABA Receptors and the Pharmacology of Sleep. In: Landolt, HP., Dijk, DJ. (eds) Sleep-Wake Neurobiology and Pharmacology . Handbook of Experimental Pharmacology, vol 253. Springer, Cham. https://doi.org/10.1007/164_2017_56

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