Neurotransmission in Epilepsy

Abstract

Summary: Some evidence indicates that in some types of focal epilepsy the enhanced excitability is due in part to impaired γ-aminobutyric acid (GABA)ergic inhibitory feedback. One form that this can take is impaired excitatory input to GABAergic interneurons. Enhanced excitatory receptor sensitivity, most characteristically involving N-methyl-D-aspartate (NMDA) receptors, has been identified in kindled rodents and in focal epilepsy in humans. Drugs that enhance GABA-mediated inhibition are anticonvulsant in many syndromes of generalized and focal epilepsy. Mechanisms through which this occurs include direct interaction with the GABAhenzodiazepine (BZD) receptor (BZDs, barbiturates, chlormethiazole), inhibition of GABA-transaminase (vigabatrin, VGB) and blocking GABA uptake (tiagabine, TGB). Glutamate receptor antagonists (both NMDA and non-NMDA antagonists) are potent anticonvulsants in many animal models of epilepsy. Whether pure glutamate receptor antagonists will have a clinical role as antiepileptic drugs (AEDs) remains to be established.