Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences

丙戊酸 癫痫发生 癫痫 神经科学 神经保护 抗惊厥药 医学 谷氨酸的 药理学 加巴喷丁 癫痫持续状态 谷氨酸受体 心理学 受体 内科学 病理 替代医学
作者
Michele Romoli,Petra Mazzocchetti,R D'Alonzo,Sabrina Siliquini,Victoria Elisa Rinaldi,Alberto Verrotti,Paolo Calabresi,Cinzia Costa
出处
期刊:Current Neuropharmacology [Bentham Science]
卷期号:17 (10): 926-946 被引量:198
标识
DOI:10.2174/1570159x17666181227165722
摘要

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.
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