Is Xenon a Future Neuroprotectant?

Pamela Sun; Jianteng Gu; Mervyn Maze; Daqing Ma


Future Neurology. 2009;14(4):483-492. 

In This Article

Mode of Action

Unlike the majority of general anesthetics, xenon exhibits little effect on GABA receptors. The mechanism by which xenon exerts anesthesia is currently unknown; however, it is understood that it is a potent and specific competitive antagonist of the subtype of the glutamate receptor, the NMDA receptor.[3,63]

The NMDA receptor is a ligand-gated ion channel, which allows the selective passage of both Na2+ and Ca2+ ions into cells. These receptors are vital in neural plasticity, learning, memory, pain and, most crucially, glutamate-mediated neurotoxicity.[64] Its activation is conditioned upon the binding of both xenon, and its coagonist glycine, at the NR1 subunit of the receptor. The essential role of glycine in this mechanism also affects the interaction in pathological conditions where the extracellular glycine concentration is high, such as in ischemia.[65]

Xenon also inhibits two other subtypes of glutamate receptor channels, namely the AMPA and KA receptors,[66] as well as the recently identified two-pore potassium channels, TREK.[67,68] Xenon is as effective as halothane in activating TREK.[69] However, its clinical relevance is yet to be clarified. Unlike halogenated volatiles, xenon also activates ATP-sensitive K + channels as reported very recently.[70]