Mechanisms of action of anticonvulsant agents

Systematic screening of many compounds in animal models led to identification of the established antiepileptic drugs (AEDs). By contrast, the newer AEDs were specifically designed to enhance an inhibitory process or to inhibit a specific excitatory pathway. However, it was later discovered that some of the designed drugs differed in their modes of action from what was envisioned. Recently, it has become apparent that all AEDs, old and new, may affect sodium and calcium channels, increase brain concentration of free γ-aminobutyric acid (GABA), and reduce glutamate-mediated excitation by inhibiting N-methyl-D-aspartate (NMDA) and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. However, not all the drugs affect all of these mechanisms. Understanding the modes of action of each drug may explain why some of them are effective in treating other neurologic and neuropsychiatric disorders. This understanding may make it possible to develop a group of neuroexcitatory amino acid transmitter antagonists with intended antiepileptogenic actions.