Valproic acid and epilepsy: from molecular mechanisms to clinical evidences.

Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr Neuropharmacol. 2018 Dec 27;: Authors: Romoli M, Mazzocchetti P, D'Alonzo R, Siliquini S, Rinaldi VE, Verrotti A, Calabresi P, Costa C Abstract 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 ...
Source: Epilepsy Curr - Category: Neurology Authors: Tags: Curr Neuropharmacol Source Type: research