Sait, LG;
Sula, A;
Ghovanloo, M-R;
Hollingworth, D;
Ruben, PC;
Wallace, BA;
(2020)
Cannabidiol interactions with voltage-gated sodium channels.
eLife
, 9
, Article e58593. 10.7554/eLife.58593.
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Abstract
Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels.
| Type: | Article |
|---|---|
| Title: | Cannabidiol interactions with voltage-gated sodium channels |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.58593 |
| Publisher version: | https://doi.org/10.7554/eLife.58593 |
| Language: | English |
| Additional information: | Copyright © 2020, Sait et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) permitting unrestricted use and redistribution provided that the original author and source are credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10113727 |
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