Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug

Wiciński, Michał; Puk, Oskar; Malinowski, Bartosz

doi:10.1007/s11064-020-03188-8

Cited by 9 publications

(4 citation statements)

References 38 publications

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“…Lev and CS pre-treatment further increased the expression of the CREB gene, and this increment is significant at CS extract at a dose of 50 mg/L ( p < 0.05). This finding establishes the neuroprotective potential of CS extract, which can similarly be seen in antiepileptic drugs such as cenobamate ( Wiciński et al, 2021 ). NPY plays a role in modulating the different processes in the brain and is expressed in multiple areas of the brain.…”

Section: Discussionsupporting

confidence: 68%

Channa Striatus Protects Against PTZ-Induced Seizures in LPS Pre-conditioned Zebrafish Model

et al. 2022

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Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Mounting evidence suggests the link between epileptogenesis and neuroinflammation. We hypothesize that eliminating neuroinflammation can alleviate seizure severity and prolong seizure onset. Channa striatus (CS) is a snakehead murrel commonly consumed by locals in Malaysia, believed to promote wound healing and mitigate inflammation. This study aims to unravel the anticonvulsive potential of CS extract on neuroinflammation-induced seizures using an adult zebrafish model. Neuroinflammation was induced via cerebroventricular microinjection of lipopolysaccharides from E. coli and later challenged with a second-hit pentylenetetrazol at a subconvulsive dose of 80 mg/kg. Zebrafish behaviour and swimming pattern analysis, as well as gene expression analysis, were done to study the pharmacological property of CS. CS extract pre-treatment in all doses significantly reduced seizure score, prolonged seizure onset time and slightly improved the locomotor swimming pattern of the zebrafish. CS extract pre-treatment at all doses significantly reduced the expression of NFKB gene in the brain, and CS extract at 25 mg/L significantly reduced the IL-1 gene expression suggesting anti-neuroinflammatory properties. However, there were no significant changes in the TNFα. Besides, CS extract at 50 mg/L also elevated the expression of the CREB gene, which exerts neuroprotective effects on the neurons and the NPY gene, which plays a role in modulating the inhibition of the excitatory neurotransmission. To sum up, CS extract demonstrated some anticonvulsive and anti-inflammatory activity on neuroinflammation-induced seizures. Still, more studies need to be done to elucidate the mechanism of action of CS extract.

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Section: Discussionsupporting

confidence: 68%

Channa Striatus Protects Against PTZ-Induced Seizures in LPS Pre-conditioned Zebrafish Model

et al. 2022

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“…Functioning not only as a blocker of voltagegated sodium channels and a positive modulator of GABA receptors, cenobamate also activates the PI3K/Akt-CREB-BDNF pathway, leading to elevated anti-apoptotic factor levels and reduced pro-apoptotic factor levels. This induction inhibits apoptosis, thereby enhancing neuronal survival (Wicinski et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Safety assessment of cenobamate: real-world adverse event analysis from the FAERS database

Chen,

Fang,

Zhao

et al. 2024

Front. Pharmacol.

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Objective:This study aims to analyze adverse drug events (ADEs) associated with cenobamate from the FAERS database, covering the third quarter of 2020 to the second quarter of 2023.Methods:Data related to cenobamate-associated ADEs from the third quarter of 2020 to the second quarter of 2023 were collected. After standardizing the data, various signal quantification techniques, including ROR, MHRA, BCPNN, and MGPS, were employed for analysis.Results:Among 2535 ADE reports where cenobamate was the primary suspected drug, 94 adverse reactions involving 11 different System Organ Class (SOC) categories were identified through the application of four signal quantification techniques. More specifically, neurological disorders and injuries resultant from complications are frequent adverse reactions associated with cenobamate.Conclusion:Our research findings align with established results, affirming the favorable safety profile of cenobamate. Effective prevention of adverse reactions induced by cenobamate can be achieved through the establishment of efficient blood concentration monitoring and dose adjustments.

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“…In this context, Wiciński et al, performed a review of the literature about the neuroprotective effects of CNB. They believe that the pharmacodynamics of CNB may confer excellent neuroprotective properties [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fourth, the inhibition of depolarization can prevent voltage-gated calcium activation, which does not allow glutamate release in the synaptic cleft and, consequently, excitotoxicity [ 110 ]. Fifth, the widespread blockade of persistent sodium currents through voltage-gated sodium channels prevents the increased depolarization and activity of central nervous system neurons [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

Cenobamate (YKP3089) and Drug-Resistant Epilepsy: A Review of the Literature

Rissardo,

Fornari Caprara

2023

Medicina

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Cenobamate (CNB), ([(R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl], is a novel tetrazole alkyl carbamate derivative. In November 2019, the Food and Drug Administration approved Xcopri®, marketed by SK Life Science Inc., (Paramus, NJ, USA) for adult focal seizures. The European Medicines Agency approved Ontozry® by Arvelle Therapeutics Netherlands B.V.(Amsterdam, The Neatherlands) in March 2021. Cenobamate is a medication that could potentially change the perspectives regarding the management and prognosis of refractory epilepsy. In this way, this study aims to review the literature on CNB’s pharmacological properties, pharmacokinetics, efficacy, and safety. CNB is a highly effective drug in managing focal onset seizures, with more than twenty percent of individuals with drug-resistant epilepsy achieving seizure freedom. This finding is remarkable in the antiseizure medication literature. The mechanism of action of CNB is still poorly understood, but it is associated with transient and persistent sodium currents and GABAergic neurotransmission. In animal studies, CNB showed sustained efficacy and potency in the 6 Hz test regardless of the stimulus intensity. CNB was revealed to be the most cost-effective drug among different third-generation antiseizure medications. Also, CNB could have neuroprotective effects. However, there are still concerns regarding its potential for abuse and suicidality risk, which future studies should clearly assess, after which protocols should be changed. The major drawback of CNB therapy is the slow and complex titration and maintenance phases preventing the wide use of this new agent in clinical practice.

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Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug

Cited by 9 publications

References 38 publications

Channa Striatus Protects Against PTZ-Induced Seizures in LPS Pre-conditioned Zebrafish Model

Channa Striatus Protects Against PTZ-Induced Seizures in LPS Pre-conditioned Zebrafish Model

Safety assessment of cenobamate: real-world adverse event analysis from the FAERS database

Cenobamate (YKP3089) and Drug-Resistant Epilepsy: A Review of the Literature

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