GABA Levels in the Brain: A Target for New Antiepileptic Drugs

Publisher Website
Google Scholar
Abstract
A basic strategy for the pharmacological treatment of epilepsy is to develop drugs that reduce the excitability of CNS neurons at times preceding or during the onset of seizure discharge with minimal effects on normal electrical activity. Several antiepileptic drugs currently in use exert their action by modulating sodium channels or receptors of the abundant inhibitory neurotransmitter, GABA. These approaches, which are often successful in reducing the number or severity of seizures, have some effects that limit their clinical use. More recently, a new class of antiepileptic drugs such as vigabatrin, which blocks GABA degradation enzymes, have been developed as effective antiepileptics and are associated with minimal side effects. Although these drugs do not display agonist or antagonist properties at GABA receptor sites, they do appear to interact with brain GABA systems because NMR spectroscopy studies indicate that subjects given these drugs have elevated brain GABA levels, and in vitro electrophysiological studies on CNS tissue reveal elevated GABA release. The precise cellular mechanisms of antiepileptic action of these GABA metabolic modulators are not clear, but current work on the cellular effects of these drugs suggests a model that may explain their action.