Role of α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptors and the antagonist perampanel in geriatric epilepsy and status epilepticus

Abstract

The α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an ionotropic glutamate receptor recognized for its active involvement in epilepsy. Through AMPAR functional alterations, multiple factors contribute to the increased susceptibility to seizures in the geriatric population. These factors include changes in the hippocampus, neuroinflammation, ischemic insults, amyloid deposition, previous seizures, alterations in the microenvironment, and neurovascular unit dysfunction. Perampanel, a noncompetitive AMPAR antagonist, has been approved for the treatment of focal and generalized epilepsy. However, a complete understanding of AMPAR's role in epileptogenesis and the pharmacotherapy of perampanel in the geriatric population remains elusive. To address this gap, we conducted a comprehensive literature review, screening 1557 articles and ultimately selecting 94 relevant ones. We provided insights into AMPAR functionality changes and perampanel's role in treating geriatric epilepsy. Various clinical trials and retrospective studies have demonstrated that the safety and efficacy of perampanel in the older population are comparable to those in the younger population, with overall good tolerability. It is also effective for treating focal and generalized onset seizures and possibly for managing status epilepticus. In conclusion, the existing body of evidence supports the safety and efficacy of perampanel in the geriatric population, indicating its potential as a valuable therapeutic option for focal and generalized epilepsy. Additional research is warranted to deepen our understanding of AMPAR's involvement in epileptogenesis and to refine the pharmacotherapeutic nuances in this specific demographic.