Chapter 25 Effects of antiepileptic drugs on the activation of glutamate receptors

Abstract

Publisher Summary Increased glutamate activation is of paramount importance in epilepsy. Epilepsy can be caused by a variety of brain disorders. Seizures, usually generalized tonicclonic seizures, can also occur during pathophysiological aberrations induced by systemic disorders such as thyreotoxicosis. The hallmark of partial seizures is the paroxysmal depolarizing shift (PDS) occurring synchronously in a large cell population when the epileptic focus is activated. The PDS is most often generated when the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors opens postsynaptic ion channels, which depolarize the cell membrane sufficiently to also trigger voltage-dependent depolarizing currents carried by calcium and sodium. Glutamatergic activation can be decreased in four different ways—namely, reducing the release of glutamate by blocking the repetitive activation of the terminals, blocking specifically the release of glutamate from the pre-synaptic terminals, blocking the activation of the postsynaptic glutamate receptors, and increasing the removal of free glutamate from the synaptic cleft. The importance of glutamatergic activation for normal brain function may also limit the usefulness of blockers of glutamate receptors.