Extensive research has failed to clarify the mechanism of action of nitrous oxide (N2O, laughing gas), a widely used inhalational anesthetic and drug of abuse. Other general anesthetics are thought to act by one of two mechanisms—blockade of NMDA glutamate receptors or enhancement of CABAergic inhibition1. Here we show that N2O, at anesthetically-relevant concentrations, inhibits both ionic currents and excitotoxic neurodegeneration mediated through NMDA receptors and, like other NMDA antagonists, produces neurotoxic side effects which can be prevented by drugs that enhance CABAergic inhibition. The favorable safety record of N2O may be explained by the low concentrations typically used and by the fact that it is usually used in combination with CABAergic anesthetics that counteract its neurotoxic potential.
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Jevtović-Todorović, V., Todorovć, S., Mennerick, S. et al. Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4, 460–463 (1998). https://doi.org/10.1038/nm0498-460
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