Excitatory Amino Acids: Approaches to Rational Anticonvulsant Therapy

In recent years, enhancement of inhibitory transmission has come to be considered the most important rational approach to the design of novel anticonvulsant drugs (Meldrum, 1983). This has led to clinical trials involving several novel compounds, designed to enhance GABA-mediated inhibition such as Progabide and Vigabatrin. The alternative approach of seeking compounds that impair excitatory transmission has only recently attracted attention. It might be thought that impairing excitatory transmission is unlikely to suppress epileptic activity selectively while leaving normal function intact. However, as will be explained below, there are reasons why it may be possible to act selectively on the sustained abnormal discharge of epilepsy.