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

Abstract

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.

Efficacy, tolerability and safety of add-on third-generation antiseizure medications in treating focal seizures worldwide: a network meta-analysis of randomised, placebo-controlled trials

“…CNB is a medication that could potentially change the perspectives regarding the management and prognosis of refractory epilepsy. 90 CNB has a dual complementary mechanism of action. It works by both inhibiting the persistent component of the sodium current, thus decreasing excitatory currents, and enhancing the inactivated state of voltage-gated sodium channels.…”

Understanding Drug-Induced Movement Disorders: Causes, Symptoms, and Treatment

“…Some antiseizure medications can cause cerebellar atrophy [46] and contribute to the development of cerebellar signs and symptoms [47]. However, some new antiseizure medications [48] have yet to be associated with movement disorders [49].…”

A Literature Review of Movement Disorder Associated with Medications and Systemic Diseases

“…Cenobamate is a relatively new antiepileptic medication approved for the treatment of focalonset seizures in adults [67]. Movement disorders, including tremors or other abnormal movements, are potential side effects of certain antiepileptic medications [68]. However, specific information on cenobamate's association with movement disorders may be limited.…”