Journal
MINI-REVIEWS IN MEDICINAL CHEMISTRY
Volume 8, Issue 1, Pages 10-23Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138955708783331568
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Since 1990 eight new antiepileptic drugs (AEDs) have been developed. Among these new drugs, Topiramate (TPM) is one of the latest AEDs available for treating drug resistant partial epilepsy both in adults and in children. The mechanisms underlying TPM antiepileptic activity are still incompletely understood. However, TPM, a sulfamate-substituted derivative of the naturally occurring monosaccharide D-fructose, has a different structure from other known AEDs. The antiepileptic activity of TPM in animal models of partial and generalized tonic-clonic seizures has been shown to be more effective as compared to other AEDs. Proposed mechanisms of action include reduction of epileptiform discharges through a voltage-dependent block of Na+ channels, enhancement of the activity of aminobutyrate at some sub-types of aminobutyrate receptors, and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors. The pharmacokinetic profile of TPM, which is characterized by its rapid and almost complete absorption after oral administration, linear pharmacokinetics, minimal protein binding and predominantly renal excretion, makes the drug a good option for the treatment. TPM was found to be effective and well tolerated in many studies conducted in adults and pediatric patients suffering from epilepsy. This review, summarising the main studies in this field, provides an overview of the current knowledge about the relevant pharmacological and clinical information on the efficacy and tolerability of TPM.
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