Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug
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REVIEW
Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug Michał Wiciński1 · Oskar Puk1 · Bartosz Malinowski1 Received: 19 July 2020 / Revised: 17 November 2020 / Accepted: 20 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 antiapoptotic 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. Keywords Cenobamate · Voltage-gated sodium channels · GABA · Secondary neuronal injury · Neuroprotection · Glutamate
Introduction Central nervous system (CNS) injuries are a great burden to health care systems around the world. In the United States alone, the annual incidence of traumatic brain injury, stroke and spinal cord injury is approximately 1.7 million, 1 million, and 15 thousand people respectively, with costs of treatment circa 100 billion US dollars per year [1–3]. In spite of the significance of this problem and the emergence of advanced therapies, the efficacy of pharmacological, neuroprotective treatment is still scarce and needs further Michał Wiciński and Oskar Puk contributed equally to this work as first co-authors. * Oskar Puk [email protected] 1
Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85‑090 Bydgoszcz, Poland
development. Although many pharmaceuticals, such as steroids and antiepileptic drugs presents neuroprotective effects, for years there were hardly any new neuroprot
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