Sait, L.G. and Sula, A. and Ghovanloo, M.-R. and Hollingworth, D. and Ruben, P.C. and Wallace, Bonnie A. (2020) Cannabidiol interactions with voltage-gated sodium channels. eLife 9 , ISSN 2050-084X.
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Abstract
Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the 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.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 11 Nov 2020 13:35 |
| Last Modified: | 02 Aug 2023 18:05 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/41438 |
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