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Fighting pain: the structure of gabapentin and its binding site in the Cavα2δ subunit

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Gabapentinoids are first-line treatments for chronic pain but are associated with adverse side effects. A cryo-EM structure of gabapentin bound to its interaction site on the calcium channel α2δ subunit now paves the way for the rational design of analgesics with greater selectivity and a reduced potential for adverse effects.

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Fig. 1: Structural insights into interactions between gabapentin and Cavα2δ and its effects on calcium channel trafficking.

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Acknowledgements

G.W.Z. is supported by research grants from the Natural Sciences and Engineering Research Council of Canada, and the Canadian Institutes of Health Research. G.W.Z. is a Canada Research Chair.

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Author notes

  1. These authors contributed equally: Laurent Ferron, Maria A. Gandini.

Authors and Affiliations

  1. Department of Clinical Neuroscience, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Laurent Ferron, Maria A. Gandini & Gerald W. Zamponi

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  1. Laurent Ferron
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  2. Maria A. Gandini
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  3. Gerald W. Zamponi
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Correspondence to Gerald W. Zamponi.

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The authors declare no competing interests.

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Ferron, L., Gandini, M.A. & Zamponi, G.W. Fighting pain: the structure of gabapentin and its binding site in the Cavα2δ subunit. Nat Struct Mol Biol 30, 717–719 (2023). https://doi.org/10.1038/s41594-023-01013-8

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