Topiramate: Its Pharmacological Properties and Therapeutic Efficacy in Epilepsy

Abstract

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 gamma-aminobutyrate at some subtypes of gamma-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.

A fatal intoxication case involving topiramate

“…1), a sulfamate-substituted monosaccharide, belongs to a novel group of anticonvulsive drugs applied in treatment of epilepsy involving Lennox-Gastaut syndrome [1,2] and in preventive therapy of migraine [3]. In addition, this substance is currently evaluated for its effectiveness in various neurological and psychiatric disorders including alcohol dependence, body weight reduction and smoking [4][5][6].…”

Therapeutic Drug Monitoring of Classical and Newer Anticonvulsants

“…Topiramate is a novel sulfamate-substituted monosaccharide AED that has multiple mechanisms of action, to include blockade of voltage-sensitive sodium channels, enhancement of GABA activity at some of the GABA-A receptors, modulation of AMPA receptor subtypes, and inhibiting carbonic anhydrase isoenzymes [129]. This AED was first approved in 1996 for the adjuvant treatment of partial and general seizures in those aged 2 years and older [130].…”

Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

“…Gabapentin (GP) is an antiepileptic drug structurally related to gamma-aminobutyric acid (GABA), for which different mechanisms of action have been suggested, such as an increase of GABA-ergic inhibition and effects on ion-gated (Na + , Ca 2+ ) and ligand-gated (GABA and glutamate receptors) ion channels [8]. Recently, binding of the compound to the voltage-gated Ca 2+ channel α2-δ1 auxiliary subunit with selective inhibitory e ect was demonstrated [9,10].…”

“…Recently, binding of the compound to the voltage-gated Ca 2+ channel α2-δ1 auxiliary subunit with selective inhibitory e ect was demonstrated [9,10]. GP was not extensively tested as a neuroprotective agent, the few existing studies have produced contradictory results, suggesting both efficiency [11][12][13][14][15] or ine ciency [16,17] having being reported [8]. A bulk of coherent evidence supports the protective role of TPM in both epilepsy [18,19] and other models of neurodegeneration [6,20,21].…”