ABSTRACT
In relation to the development of a number of neurodegenerative diseases, hypoactivity of GABA and/or hyperactivity of Glu neuronal functions seem to be involved. Neurodegenerative disorders such as epilepsy, Huntington’s chorea, Parkinson’s disease, AIDS dementia and amyotrophic lateral sclerosis are examples of progressive diseases, where compounds interacting with the GABAergic and/or glutamatergic receptor systems may be of therapeutic value. Analysis of brain tissue samples from sites near seizure foci in epileptic patients or from animal models of epilepsy have revealed severe impairment of the GABAergic system. Reduction in the level of the GABA-synthesizing enzyme, Glu decarboxylase (GAD) (Figure 9.2) has been reported as well as reduction in the number of and/or efficiency of GABA transporters in models of epilepsy. Pharmacological studies have shown compounds enhancing GABA levels to be anticonvulsive and compounds with the reverse action to be convulsive. Similar studies using Glu receptor active compounds have shown the opposite effects in animal seizure models, convulsive action of agonists and anticonvulsive action of antagonists.
