Novel Mechanisms of Action of Three Antiepileptic Drugs, Vigabatrin, Tiagabine, and Topiramate
- 1 February 2003
- journal article
- review article
- Published by Springer Science and Business Media LLC in Neurochemical Research
- Vol. 28 (2), 333-340
- https://doi.org/10.1023/a:1022393604014
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 Ca2+-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.Keywords
This publication has 60 references indexed in Scilit:
- Two new actions of topiramate: inhibition of depolarizing GABAA-mediated responses and activation of a potassium conductanceNeuropharmacology, 2002
- Nonfocal Generalized Tonic–Clonic Seizures: Response During Long‐Term Topiramate TreatmentEpilepsia, 2000
- Transient Inhibition of Glutamate Uptake In Vivo Induces Neurodegeneration when Energy Metabolism Is ImpairedJournal of Neurochemistry, 1999
- Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human BrainEpilepsia, 1995
- Topiramate: Preclinical Evaluation of a Structurally Novel AnticonvulsantEpilepsia, 1994
- Metabolic manipulation of neural tissue to counter the hypersynchronous excitation of migraine and epilepsyNeurochemical Research, 1993
- On the epileptogenic effects of kainic acid and dihydrokainic acid in the dentate gyrus of the ratNeuropharmacology, 1988
- Double‐Blind Dose Reduction Study of Vigabatrin in Complex Partial EpilepsyEpilepsia, 1987
- Increased gamma-aminobutyric acid (GABA), homocarnosine and β-alanine in cerebrospinal fluid of patients treated with γ-vinyl GABA (4-amino-hex-5-enoic acid)Life Sciences, 1981
- OCCLUSION AND METABOLISM OF γ‐AMINOBUTYRIC ACID BY BRAIN TISSUE*Journal of Neurochemistry, 1958