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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References
Field, M. J. et al. Proc. Natl Acad. Sci USA 103, 17537–17542 (2006).
Marais, E., Klugbauer, N. & Hofmann, F. Mol. Pharmacol. 59, 1243–1248 (2001).
Davies, A. et al. Proc. Natl Acad. Sci USA 107, 1654–1659 (2010).
Wu, J. et al. Nature 537, 191–196 (2016).
Nieto-Rostro, M., Ramgoolam, K., Pratt, W. S., Kulik, A. & Dolphin, A. C. Proc. Natl Acad. Sci. USA 115, E12043–E12052 (2018).
Nieto-Rostro, M., Patel, R., Dickenson, A. H. & Dolphin, A. C. Pain 64, 1264–1279 (2023).
Chen, Z., Mondal, A. & Minor, D. L. Jr. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-023-00951-7 (2023).
Chen, Z. et al. Nature https://doi.org/10.1038/s41586-023-06175-5 (in the press).
Wang, M., Offord, J., Oxender, D. L. & Su, T. Z. Biochem. J. 342, 313–320 (1999).
Gumerov, V. M. et al. Proc. Natl Acad. Sci. USA 119, e2110415119 (2022).
Page, K. M., Gumerov, V. M., Dahimene, S., Zhulin, I. B. & Dolphin, A. C. Channels (Austin) 17, 2167563 (2023).
Gao, S., Yao, X. & Yan, N. Nature 596, 143–147 (2021).
Tran-Van-Minh, A. & Dolphin, A. C. J. Neurosci. 30, 12856–12867 (2010).
Goodman, C. W. & Brett, A. S. JAMA Intern. Med. 179, 695–701 (2019).
Keppel Hesselink, J. M. Int. J. Clin. Pharmacol. 1, 1–3 (2016).
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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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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DOI: https://doi.org/10.1038/s41594-023-01013-8
