Excitotoxicity is the pathological process by which [[nerve cell]]s are damaged or killed by excessive stimulation by [[neurotransmitter]]s such as [[glutamate]] and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the [[NMDA]] receptor and [[AMPA]] receptor are overactivated by glutamatergic storm. Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell.

Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as [[calpain]]. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.