Azo-Propofols: Photochromic Potentiators of GABAA Receptors

Authors

  • Marco Stein,

    1. Department of Chemistry, Ludwig-Maximilians-Universität, München and Center of Integrated Protein Science, 81377 Munich (Germany)
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    • These authors contributed equally to this work.

  • Simon J. Middendorp,

    1. Institute for Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern (Switzerland)
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    • These authors contributed equally to this work.

  • Valentina Carta,

    1. Institute for Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern (Switzerland)
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  • Ervin Pejo,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114 (USA)
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  • Douglas E. Raines,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114 (USA)
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  • Stuart A. Forman,

    1. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114 (USA)
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  • Erwin Sigel,

    Corresponding author
    1. Institute for Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern (Switzerland)
    • Institute for Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern (Switzerland)
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  • Dirk Trauner

    Corresponding author
    1. Department of Chemistry, Ludwig-Maximilians-Universität, München and Center of Integrated Protein Science, 81377 Munich (Germany)
    • Department of Chemistry, Ludwig-Maximilians-Universität, München and Center of Integrated Protein Science, 81377 Munich (Germany)
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  • We thank Dr. Peter Mayer (LMU Munich) for the determination of the X-ray structure. M. S. is grateful to the Fonds der Chemischen Industrie for a Ph.D. fellowship. This work was supported by the Swiss National Science Foundation grants 31003A-132806/1 (E.S.) and the European Science Foundation (ERC grant No 268795 to D.T.) and the National Institutes of Health (GM089745 to S.A.F and GM087316 to D.E.R.). GABA=γ-aminobutyric acid.

Abstract

original image

Shine and rise! GABAA receptors are ligand-gated chloride ion channels that respond to γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter of the mammalian central nervous system. Azobenzene derivatives of propofol, such as compound 1 (see scheme), increase GABA-induced currents in the dark form and lose this property upon light exposure and thus function as photochromic potentiators. Compound 1 can be employed as a light-dependent general anesthetic in translucent tadpoles.

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