Pharmacophore model for antiepileptic drugs acting on sodium channels

Fifteen antiepileptic drugs (AED), active against the maximal electroshock seizure test and able to block the neuronal voltage-dependent sodium channe l, have been studied by means of a similarity analysis. Structural and elec tronic, quantum chemically derived characteristics are compared. Rigid anal ogs are included, because of the flexibility of some structures, in order t o discern the conformational requirements associated with these ligands in the moment of the interaction. An inactive compound (ethosuximide) helps in the definition of the structural factors that are important for the activi ty. We propose a pharmacophore model that, giving an interpretation of the biological activity, allows the design of new AED with a well-defined mecha nism of interaction.