In vitro effects of eslicarbazepine (S-licarbazepine) as a potential precision therapy on SCN8A variants causing neuropsychiatric disorders.
NaV1.6
S-licarbazepine
SCN8A
developmental and epileptic encephalopathy
epilepsy
eslicarbazepine
precision medicine
sodium channel blocker
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
06
10
2022
received:
20
08
2021
accepted:
07
10
2022
pubmed:
3
11
2022
medline:
15
3
2023
entrez:
2
11
2022
Statut:
ppublish
Résumé
Variants in SCN8A, the Na We investigated the therapeutic potential of eslicarbazepine (S-licarbazepine; S-lic), an enhancer of slow inactivation of voltage gated sodium channels, on two variants with biophysical and neuronal gain-of-function (G1475R and M1760I) and one variant with biophysical gain-of-function but neuronal loss-of-function (A1622D) in neuroblastoma cells and in murine primary hippocampal neuron cultures. These three variants cover the broad spectrum of Na Similar to known effects on Na S-lic has not only substance-specific effects but also variant-specific effects. Personalized treatment regimens optimized to achieve such variant-specific pharmacological modulation may help to reduce adverse side effects and improve the overall therapeutic outcome of SCN8A-related disease.
Sections du résumé
BACKGROUND AND PURPOSE
Variants in SCN8A, the Na
EXPERIMENTAL APPROACH
We investigated the therapeutic potential of eslicarbazepine (S-licarbazepine; S-lic), an enhancer of slow inactivation of voltage gated sodium channels, on two variants with biophysical and neuronal gain-of-function (G1475R and M1760I) and one variant with biophysical gain-of-function but neuronal loss-of-function (A1622D) in neuroblastoma cells and in murine primary hippocampal neuron cultures. These three variants cover the broad spectrum of Na
KEY RESULTS
Similar to known effects on Na
CONCLUSIONS AND IMPLICATIONS
S-lic has not only substance-specific effects but also variant-specific effects. Personalized treatment regimens optimized to achieve such variant-specific pharmacological modulation may help to reduce adverse side effects and improve the overall therapeutic outcome of SCN8A-related disease.
Substances chimiques
eslicarbazepine
S5VXA428R4
10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide
XFX1A5KJ3V
Dibenzazepines
0
NAV1.6 Voltage-Gated Sodium Channel
0
Scn8a protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1038-1055Informations de copyright
© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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