J A Armijo1, J Adin, M B Sánchez. 1. Hospital Universitario Marques de Valdecilla, 39008 Santander, Espana. facasj@humv.es
Abstract
INTRODUCTION: Although 10 second generation new antiepileptic drugs are currently available on the market, 30% of patients are resistant to pharmacological treatment. In addition, today's antiepileptic drugs avert or suppress seizures but do not prevent the appearance of epilepsy or its progression. DEVELOPMENT: The foundations of the aetiopathogenesis of epilepsy and the main targets of antiepileptic drugs are described. Describing the important role of gamma-aminobutyric and glutamic acid in the genesis and proliferation of the seizures has allowed for the development of new antiepileptic drugs that increase the inhibitory tone of GABA or inhibit the excitatory tone of glutamate. The discovery that some epilepsies may be due to channelopathies is now making it possible to conduct research into drugs that inhibit calcium channels, activate potassium channels or inhibit abnormal AMPA/KA receptor channels. Recent reports describing a specific attachment of some antiepileptic drugs to the a2d subunits of the calcium channel and to the synaptic vesicles proteins SV2A open up new perspectives. Moreover, research is also being carried out on new drugs that are capable of preventing epileptogenesis, stemming the progression of epilepsy or overcoming the resistance to pharmacological treatment displayed by some epilepsies. CONCLUSIONS: The identification of new pharmacological targets in the aetiopathogenesis of epilepsies has made it possible to develop second generation antiepileptic drugs and it is allowing for the development of third generation antiepileptic drugs.
INTRODUCTION: Although 10 second generation new antiepileptic drugs are currently available on the market, 30% of patients are resistant to pharmacological treatment. In addition, today's antiepileptic drugs avert or suppress seizures but do not prevent the appearance of epilepsy or its progression. DEVELOPMENT: The foundations of the aetiopathogenesis of epilepsy and the main targets of antiepileptic drugs are described. Describing the important role of gamma-aminobutyric and glutamic acid in the genesis and proliferation of the seizures has allowed for the development of new antiepileptic drugs that increase the inhibitory tone of GABA or inhibit the excitatory tone of glutamate. The discovery that some epilepsies may be due to channelopathies is now making it possible to conduct research into drugs that inhibit calcium channels, activate potassium channels or inhibit abnormal AMPA/KA receptor channels. Recent reports describing a specific attachment of some antiepileptic drugs to the a2d subunits of the calcium channel and to the synaptic vesicles proteins SV2A open up new perspectives. Moreover, research is also being carried out on new drugs that are capable of preventing epileptogenesis, stemming the progression of epilepsy or overcoming the resistance to pharmacological treatment displayed by some epilepsies. CONCLUSIONS: The identification of new pharmacological targets in the aetiopathogenesis of epilepsies has made it possible to develop second generation antiepileptic drugs and it is allowing for the development of third generation antiepileptic drugs.