Novel mechanisms of action of three antiepileptic drugs, vigabatrin, tiagabine, and topiramate

Abstract

Epilepsy, a functional disturbance of the CNS and induced by abnormal electrical discharges, manifests by recurrent seizures. Although new antiepileptic drugs have been developed during recent years, still more than one third of patients with epilepsy are refractory to treatment. Therefore, the search for new mechanisms that can regulate cellular excitability are of utmost importance. Three currently available drugs are of special interest because they have novel mechanisms of action and are especially effective for partial onset seizures. Vigabatrin is a selective and irreversible GABA-transaminase inhibitor that greatly increases whole-brain levels of GABA. Tiagabine is a potent inhibitor of GABA uptake into neurons and glial cells. Topiramate is considered to produce its antiepileptic effect through several mechanisms, including modification of Na(+)-and/or Ca(2+)-dependent action potentials, enhancement of GABA-mediated Cl- fluxes into neurons, and inhibition of kainate-mediated conductance at glutamate receptors of the AMPA/kainate type. This review will discuss these mechanisms of action at the cellular and molecular levels.