Glutamate and GABA synthesis, release, transport and metabolism as targets for seizure control

The synthesis, release, reuptake, and metabolism of the excitatory and inhibitory neurotransmitters glutamate and GABA, respectively, are tightly controlled. Given the role that these two neurotransmitters play in normal and abnormal neurotransmission, it is important to consider the processes whereby they are regulated. This brief review is focused entirely on the metabolic aspects of glutamate and GABA synthesis and neurotransmission. It describes in limited detail the synthesis, release, reuptake, metabolism, cellular compartmentation and pharmacology of the glutamatergic and GABAergic synapse. This review also provides a summary and brief description of the pathologic and phenotypic features of the various genetic animal models that have been developed in an effort to provide a greater understanding of the role that each of the aforementioned metabolic processes plays in controlling excitatory and inhibitory neurotransmission and how their use will hopefully facilitate the development of safer and more efficacious therapies for the treatment of epilepsy and other neurological disorders.

► Synthesis, packaging, release, and termination of neurotransmitters alter activity. ► Metabolizing enzymes and membrane transporters are integral therapeutic targets. ► Genetically altered mice offer insight into the roles of GABA/glutamate. ► GABA and glutamate are targets for antiepileptic and neuroprotective therapies.