Cenobamate, a New Promising Antiseizure Medication: Experimental and Clinical Aspects

About 40-50% of patients with drug-resistant epilepsy do not properly respond to pharmacological therapy with antiseizure medications (ASMs). Recently approved by the US Food and Drug Administration and European Medicines Agency as an add-on drug for focal seizures, cenobamate is an ASM sharing two basic mechanisms of action and exhibiting a promising profile of clinical efficacy. The drug preferably inhibits persistent sodium current and activates GABA-mediated events via extrasynaptic, non-benzodiazepine receptors. Thus, its antiseizure potential is dependent on both reducing excitation and enhancing inhibition in the central nervous system. In experimental seizure models, cenobamate exhibited a clear-cut activity in many of them with promising protective indexes, with only bicuculline-induced seizures being unaffected. Randomized clinical trials indicate that combinations of cenobamate, with already prescribed ASMs, resulted in significant percentages of seizure-free patients and patients with a significant reduction in seizure frequency, compared to other ASMs in the form of an add-on therapy. Its greater antiseizure efficacy was accompanied by adverse events comparable to other ASMs. Cenobamate has also been shown to possess neuroprotective activity, which may be of importance in affecting the process of epileptogenesis and, thus, modifying the course of epilepsy.