Assessment of epileptogenic potential: experimental, clinical and epidemiological approaches

There are experimental, clinical and epidemiological methods of assessing the epileptogenic potential of psychotropic drugs. In the laboratory it has been shown that there is a range of cellular and synaptic processes in the cerebral cortex and hippocampus that give rise to epileptiform neuronal activity. In addition to the classical suppression of GABA-mediated inhibitory synaptic mechanisms, in vitro studies in animal models of epilepsy and on human tissue suggest a prominent role for the N-methyl D-aspartate (NMDA) subtype of excitatory amino acid receptors. Any mechanism that leads to the depolarization of the neurones is likely to result in a facilitation of the NMDA-receptor involvement in excitatory neurotransmission. This is particularly true in the cortex and hippocampus where the densities of the NMDA-receptor are highest. Data are presented in this paper on how this epileptogenic mechanism can be studied in vitro. In humans, the importance of an accurate diagnosis is stressed and the advantages and disadvantages of routine EEG recordings and ambulatory monitoring discussed. Descriptions of large-scale systems of drug safety monitoring and their application to the assessment of the epileptogenic properties of psychotropic drugs are given.