NITROUS-OXIDE (LAUGHING GAS) IS AN NMDA ANTAGONIST, NEUROPROTECTANT AND NEUROTOXIN

Extensive research has failed to clarify the mechanism of action of ni trous oxide (N2O, laughing gas), a widely used inhalational anesthetic and drug of abuse. Other general anesthetics are thought to act by on e of two mechanisms-blockade of NMDA glutamate receptors or enhancemen t of GABAergic inhibition(1). Here we show that N2O, at anesthetically -relevant concentrations, inhibits both ionic currents and excitotoxic neurodegeneration mediated through NMDA receptors and, like other NMD A antagonists, produces neurotoxic side effects which can be prevented by drugs that enhance GABAergic inhibition. The favorable safety reco rd of N2O may be explained by the low concentrations typically used an d by the fact that it is usually used in combination with GABAergic an esthetics that counteract its neurotoxic potential.