Significance of Glutamate Receptor, Especially AMPA/KA Receptors, in Epilepsy and Antiepileptic Effects of Novel Antiepileptic Drug, Topiramate

Abstract

Epileptogenesis is induced by repeated seizures attributed to several kinds of causes following the initial exposure to exogenesis factors (i.e. brain trauma, etc.) and/or endogeneous factors (such as gene abnormalities). Under the establishment of epileptogenesis, epileptic seizures are induced by hypersynchronization of neuronal groups due to abnormal activities of voltage-dependent and/or receptor-activated ion channels. In the above-mentioned epileptogenesis, partial mutation of the AMPA/KA receptor-channel complex induces both Ca²⁺and Na⁺influxes, thereby producing epileptic seizures and/or neuronal death.
Currently available antiepileptic drugs act as inhibitors of the Na⁺or T/L/PQ type Ca²⁺channels, modulators of K⁺channels or GABA_A receptor agonists/enhancers. Recently, antagonists of the AMPA/KA receptor, such as topiramate and talampanel, have been found to display a novel antiepileptic mechanism. Unlike other conventional antiepileptics, topiramate elicits a dual functional characteristic that inhibits neuronal death while exhibiting an antiepileptic (anti-seizure) effect.