Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences.
Valproic acid
epigenetics
epilepsy
epileptogenesis
neuroprotection
pharmacology.
Journal
Current neuropharmacology
ISSN: 1875-6190
Titre abrégé: Curr Neuropharmacol
Pays: United Arab Emirates
ID NLM: 101157239
Informations de publication
Date de publication:
2019
2019
Historique:
received:
25
10
2018
revised:
03
12
2018
accepted:
20
12
2018
pubmed:
29
12
2018
medline:
20
2
2020
entrez:
29
12
2018
Statut:
ppublish
Résumé
After more than a century from its discovery, valproic acid (VPA) still represents one of the most efficient antiepileptic drugs (AEDs). Pre and post-synaptic effects of VPA depend on a very broad spectrum of actions, including the regulation of ionic currents and the facilitation of GABAergic over glutamatergic transmission. As a result, VPA indirectly modulates neurotransmitter release and strengthens the threshold for seizure activity. However, even though participating to the anticonvulsant action, such mechanisms seem to have minor impact on epileptogenesis. Nonetheless, VPA has been reported to exert anti-epileptogenic effects. Epigenetic mechanisms, including histone deacetylases (HDACs), BDNF and GDNF modulation are pivotal to orientate neurons toward a neuroprotective status and promote dendritic spines organization. From such broad spectrum of actions comes constantly enlarging indications for VPA. It represents a drug of choice in child and adult with epilepsy, with either general or focal seizures, and is a consistent and safe IV option in generalized convulsive status epilepticus. Moreover, since VPA modulates DNA transcription through HDACs, recent evidences point to its use as an anti-nociceptive in migraine prophylaxis, and, even more interestingly, as a positive modulator of chemotherapy in cancer treatment. Furthermore, VPA-induced neuroprotection is under investigation for benefit in stroke and traumatic brain injury. Hence, VPA has still got its place in epilepsy, and yet deserves attention for its use far beyond neurological diseases. In this review, we aim to highlight, with a translational intent, the molecular basis and the clinical indications of VPA.
Identifiants
pubmed: 30592252
pii: CN-EPUB-95475
doi: 10.2174/1570159X17666181227165722
pmc: PMC7052829
doi:
Substances chimiques
Anticonvulsants
0
Valproic Acid
614OI1Z5WI
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
926-946Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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