Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug

• Published in: Neurochemical research Vol. 46; no. 3; pp. 439 - 446
• Main Authors: Wiciński, Michał, Puk, Oskar, Malinowski, Bartosz
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2021; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antiepileptic agents; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Cell Biology; Central nervous system; Cyclic AMP response element-binding protein; Injury prevention; Nervous system; Nervous tissues; Neurochemistry; Neurological diseases; Neurology; Neuroprotection; Neurosciences; Neurosurgery; Regeneration; Review; Sodium channels (voltage-gated); Trauma; γ-Aminobutyric acid A receptors; United States > US; GABA; Secondary neuronal injury; Neuroprotection; Glutamate; Cenobamate; Voltage-gated sodium channels
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-020-03188-8

Central nervous system (CNS) injuries annually afflict approximately 2.7 million people in United States only, inflicting costs of nearly 100 billion US dollars. The gravity of this problem is a consequence of severe and prolonged disability of patients due to a scarce regeneration of CNS, along with the lack of efficient neuroprotective and neuroregenrative therapies. Therefore, the first and most important task in managing the CNS injury is reduction of the damaged area, and apoptosis of neurons occurs not only during the trauma, but in great extent within the following minutes and hours. This process, called secondary injury phase, is a result of trauma-induced metabolic changes in nervous tissue and neuron apoptosis. Cenobamate is a new antiepileptic drug approved by FDA on November 21, 2019. Regardless of its primary purpose, cenobamate, as a blocker of voltage-gated sodium channels and positive modulator of GABAa receptors, it appears to be a promising neuroprotective agent. Moreover, through activation of PI3K/Akt-CREB-BDNF pathway, it leads to the increase of anti-apoptotic factor levels and the decrease of pro-apoptotic factor levels, which induce inhibition of apoptosis and increase neuron survival. Similarly to riluzole, cenobamate could be an important part of a perioperative procedure in neurosurgery, decreasing the occurrence of neurological deficits. Provided that cenobamate will be effective in aforementioned conditions, it could improve treatment outcomes of millions of patients every year, thereby an extensive investigation of its efficacy as a neuroprotective treatment after central nervous system trauma should follow.