New Strategies in Therapeutic Targets of Epilepsy

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 August 2024 | Viewed by 1573

Special Issue Editor


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Guest Editor
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA
Interests: drug development; sudden unexpected death in epilepsy; Dravet syndrome

Special Issue Information

Dear Colleagues,

We have been fortunate to see new drugs with diverse mechanisms of action enter into clinical use for epilepsy in recent years. However, as many of us are aware, we have not been able to reduce the proportion of individuals with epilepsy whose seizures are not fully controlled. Nevertheless, exciting ongoing efforts continue to identify and validate novel targets and therapeutic approaches. This Special Issue will be focused on new strategies for identifying and validating therapeutic targets for epilepsy. This will include, but is not limited to, (1) novel mechanisms for the treatment of epilepsy and its comorbidities; (2) novel tools and approaches in target identification/validation, drug screening/differentiation, tolerability assessment and de-risking of potential therapies; and (3) novel targets and/or approaches for disease-modifying or anti-epileptogenic therapies. Articles within these general areas may be focused on unique populations (e.g., rare epilepsies) or may be applicable to a wider range of epilepsy disorders. 

We hope that you will consider submitting to this Special Issue.

Dr. Cameron S. Metcalf
Guest Editor

Manuscript Submission Information

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Keywords

  • drug development
  • animal models
  • epilepsy
  • seizure
  • rare epilepsy
  • traumatic brain injury
  • epileptogenesis
  • disease modification
  • drug discovery

Published Papers (1 paper)

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Research

16 pages, 2881 KiB  
Article
Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with Δ9-THC through the 5-HT1A Receptor in the Neocortex of Mice
by Yasaman Javadzadeh, Alexandra Santos, Mark S. Aquilino, Shanthini Mylvaganam, Karolina Urban and Peter L. Carlen
Cells 2024, 13(6), 466; https://doi.org/10.3390/cells13060466 - 7 Mar 2024
Viewed by 1405
Abstract
Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9-THC), [...] Read more.
Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9-THC), as well as (iii) the serotonin (5-HT)1A receptor’s role in CBD’s mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices. The anticonvulsant effect of 10, 30, and 100 µM CBD alone and combined with Δ9-THC was evaluated. To examine CBD’s mechanism of action, slices were pre-treated with a 5-HT1A receptor antagonist before CBD’s effect was evaluated. An amount of ≥30 µM CBD alone exerted significant anticonvulsant effects while 10 µM CBD did not. However, 10 µM CBD combined with low-dose Δ9-THC (20:3 ratio) displayed significantly greater anticonvulsant effects than either phytocannabinoid alone. Furthermore, blocking 5-HT1A receptors before CBD application significantly abolished CBD’s effects. Thus, our results demonstrate the efficacy of low-dose CBD and Δ9-THC combined and that CBD exerts its effects, at least in part, through 5-HT1A receptors. These results could address drug-resistance while providing insight into CBD’s mechanism of action, laying the groundwork for further testing of cannabinoids as anticonvulsants. Full article
(This article belongs to the Special Issue New Strategies in Therapeutic Targets of Epilepsy)
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