Target pharmacology of topiramate, a new antiepileptic drug

Abstract

Topiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. Since topiramate hardly affects the threshold of the seizure, topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (γ-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/α-amino-3- hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.