Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications

Abstract

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient's quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABA_A ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events.

Keywords: Cenobamate; GABAA ion channels; XCOPRI; antiepileptic drug; epilepsy; partial seizures; sulfamoylphenyl moieties.