Literature DB >> 33252771

Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug.

Michał Wiciński1, Oskar Puk2, Bartosz Malinowski1.   

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 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.

Entities:  

Keywords:  Cenobamate; GABA; Glutamate; Neuroprotection; Secondary neuronal injury; Voltage-gated sodium channels

Year:  2020        PMID: 33252771     DOI: 10.1007/s11064-020-03188-8

Source DB:  PubMed          Journal:  Neurochem Res        ISSN: 0364-3190            Impact factor:   3.996


  29 in total

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Authors:  Asla Pitkänen; Hana Kubova
Journal:  Expert Opin Pharmacother       Date:  2004-04       Impact factor: 3.889

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Authors:  Meir Bialer; Svein I Johannessen; René H Levy; Emilio Perucca; Torbjörn Tomson; H Steve White
Journal:  Epilepsy Res       Date:  2010-12       Impact factor: 3.045

Review 3.  Cenobamate: First Approval.

Authors:  Susan J Keam
Journal:  Drugs       Date:  2020-01       Impact factor: 9.546

Review 4.  Riluzole for acute traumatic spinal cord injury: a promising neuroprotective treatment strategy.

Authors:  Jefferson R Wilson; Michael G Fehlings
Journal:  World Neurosurg       Date:  2013-01-04       Impact factor: 2.104

Review 5.  Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI).

Authors:  Meir Bialer; Svein I Johannessen; René H Levy; Emilio Perucca; Torbjörn Tomson; H Steve White
Journal:  Epilepsy Res       Date:  2012-12-04       Impact factor: 3.045

Review 6.  Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability.

Authors:  Balázs Pál
Journal:  Cell Mol Life Sci       Date:  2018-05-15       Impact factor: 9.261

7.  Mechanisms of secondary injury to spinal cord axons in vitro: role of Na+, Na(+)-K(+)-ATPase, the Na(+)-H+ exchanger, and the Na(+)-Ca2+ exchanger.

Authors:  S K Agrawal; M G Fehlings
Journal:  J Neurosci       Date:  1996-01-15       Impact factor: 6.167

Review 8.  Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.

Authors:  Matthew L Pearn; Ingrid R Niesman; Junji Egawa; Atsushi Sawada; Angels Almenar-Queralt; Sameer B Shah; Josh L Duckworth; Brian P Head
Journal:  Cell Mol Neurobiol       Date:  2016-07-06       Impact factor: 5.046

Review 9.  Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside.

Authors:  Narihito Nagoshi; Hiroaki Nakashima; Michael G Fehlings
Journal:  Molecules       Date:  2015-04-29       Impact factor: 4.411

Review 10.  Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders.

Authors:  Giles E Hardingham; Hilmar Bading
Journal:  Nat Rev Neurosci       Date:  2010-09-15       Impact factor: 34.870

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Review 2.  The Interconnected Mechanisms of Oxidative Stress and Neuroinflammation in Epilepsy.

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