antiexcitotoxic

Antiexcitotoxic refers to agents and strategies that protect neurons from excitotoxic injury by limiting the deleterious effects of excessive glutamatergic signaling. Excitotoxicity occurs when overactivation of glutamate receptors, especially NMDA receptors, leads to sustained calcium influx, activation of proteolytic enzymes, mitochondrial dysfunction, oxidative stress, and ultimately neuronal death. Antiexcitotoxic interventions aim to interrupt this cascade by reducing receptor activation, enhancing glutamate clearance, or otherwise stabilizing intracellular calcium and energy metabolism.

Common approaches include pharmacologic antagonism of NMDA and other ionotropic glutamate receptors, partial antagonism to preserve normal physiological signaling (as with memantine), blockade or modulation of AMPA/kainate receptors, augmentation of astrocytic glutamate uptake, calcium chelation, and antioxidant strategies. Some endogenous or dietary compounds, such as kynurenic acid, act as receptor antagonists and are studied for their protective potential.

Clinical use: NMDA receptor antagonists have shown neuroprotective effects in preclinical models but have yielded limited, sometimes adverse, results in human trials for acute brain injury and stroke. Memantine is approved for Alzheimer's disease and has a relatively favorable safety profile, but its antiexcitotoxic effects in acute injury are not the primary indication. Magnesium sulfate and other agents have been explored for neuroprotection with mixed results. Overall, antiexcitotoxic therapy remains an area of active research, with ongoing investigation into dosing, timing, and combination therapies to maximize benefit while minimizing side effects.

See also: excitotoxicity, neuroprotection, NMDA receptor antagonist.