New antiepileptic drugs: molecular targets.
In the past 20 years, a number of new antiepileptic drugs (AEDs) have been introduced and other molecules are in development, some of which are advantageous in terms of pharmacokinetics, tolerability and potential for drug interactions. These drugs are regarded as second generation compared to older agents such as barbiturates, phenytoin, carbamazepine, ethosuximide and valproic acid. Although some of these second generation compounds may be advantageous in terms of kinetics, tolerability and potential for drug interactions, all of them still target voltage-gated channels or GABA-mediated inhibition, predominantly, without any real improvement in epilepsy therapy. Studies on mechanisms of seizure generation and propagation have identified new potential targets for AEDs. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies. In this review the molecular targets for new AEDs are discussed, providing further suggestions on how future research can be improved.
Mula
Marco
M
Department of Clinical & Experimental Medicine, Section of Neurology, Amedeo Avogadro University, Corso Mazzini 18, Novara, Italy. marco.mula@med.unipmn.it
D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000627:therapeutic use; D001463:Barbiturates / Q000008:administration & dosage / Q000627:therapeutic use; D002220:Carbamazepine / Q000008:administration & dosage* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D005013:Ethosuximide / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D050479:Neurotransmitter Transport Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D010672:Phenytoin / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D012640:Seizures / Q000628:therapy*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000627:therapeutic use
D000927:Anticonvulsants; D001463:Barbiturates; D050479:Neurotransmitter Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D005013:Ethosuximide; D014635:Valproic Acid; D010672:Phenytoin