Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin
Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin
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DOI：
10.1038/nm0498-460
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发表时间：
1998-04-01
期刊：
影响因子：
82.9
通讯作者：
Olney, JW
中科院分区：
文献类型：
--
作者：
Jevtovic-Todorovic, V;Todorovic, SM;Olney, JW
大量研究未能阐明一氧化二氮（N2O，笑气）的作用机制，一氧化二氮是一种广泛使用的吸入麻醉剂和滥用药物。其他全身麻醉剂被认为是通过两种机制之一起作用 - 阻断 NMDA 谷氨酸受体或增强 GABA 能抑制 (1)。在这里，我们表明，N2O 在麻醉相关浓度下，可抑制通过 NMDA 受体介导的离子电流和兴奋性神经变性，并且与其他 NMDA 拮抗剂一样，会产生神经毒性副作用，而增强 GABA 能抑制的药物可以预防这种副作用。 N2O 良好的安全记录可能是因为通常使用的浓度较低，而且它通常与 GABA 麻醉剂联合使用，以抵消其潜在的神经毒性。
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 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 NMDA antagonists, produces neurotoxic side effects which can be prevented by drugs that enhance GABAergic 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 GABAergic anesthetics that counteract its neurotoxic potential.