Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon
Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon
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DOI：
10.1196/annals.1344.025
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Lemaire, M
中科院分区：
文献类型：
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作者：
Abraini, JH;David, HN;Lemaire, M
尽管原型谷氨酸能受体拮抗剂在动物模型中具有有益的效果，但是通过使用这种药剂的药理学尝试已经遇到了非常有限的临床成功，因为这些化合物产生不利的副作用并且在神经保护和治疗浓度下具有内在的神经毒性。有趣的是，一氧化二氮和氙气，这是一种非常安全的临床麻醉气体，已被证明是有效的NMDA受体抑制剂。我们简要回顾了积累的证据表明，一氧化二氮和氙在亚麻醉浓度可能有潜在的神经保护和治疗特性，特别关注其有益的影响缺血诱导的神经元死亡和安非他明诱导的敏化。75体积%的一氧化二氮和高达70体积%的氙可减少啮齿动物大脑中动脉闭塞引起的缺血诱导的神经元死亡，并减少神经元细胞培养物中NMDA诱导的Ca2+内流，这是兴奋性毒性中涉及的关键事件。75体积%的一氧化二氮和50体积%的氙气进一步降低了安非他明诱导的啮齿动物运动致敏作用。然而，在75体积%的较高浓度下，氙显示出潜在的神经毒性和不良副作用。由于这两种药物都能迅速从体内消除，因此与原型NMDA受体拮抗剂相比，以适当的亚麻醉神经保护和治疗浓度给药可能不会产生不良副作用和潜在的神经毒性。最后，在人类可能的治疗意义进行了讨论。
Despite the beneficial effects of prototypical glutamatergic receptor antagonists in animal models, the pharmacological attempts by the use of such agents have met with very limited clinical success because these compounds produce adverse side effects and possess an intrinsic neurotoxicity at neuroprotective and therapeutic concentrations. Interestingly, nitrous oxide and xenon, which are anesthetic gases with a remarkably safe clinical profile, have been shown to be effective inhibitors of the NMDA receptor. We briefly review accumulating evidence that nitrous oxide and xenon at subanesthetic concentrations may have potentially neuroprotective and therapeutic properties, with a particular focus on their beneficial effects on ischemia-induced neuronal death and amphetamine-induced sensitization. Nitrous oxide at 75-vol% and xenon up to 70-vol% reduce ischemia-induced neuronal death induced by occlusion of the middle cerebral artery in rodents, and decrease NMDA-induced Ca2+ influx in neuronal cell cultures, a critical event involved in excitotoxicity. Nitrous oxide at 75-vol % and xenon at 50-vol % further reduced amphetamine-induced locomotor sensitization in rodents. However, at a higher concentration of 75-vol %, xenon shows potentially neurotoxic properties and adverse side effects. Because both agents are rapidly eliminated from the body, it is plausible that their administration at appropriate subanesthetic neuroprotective and therapeutic concentrations may not be associated, in contrast with prototypical NMDA receptor antagonists, with adverse side effects and potentially neurotoxicity. Finally, the possible therapeutic implications in humans are discussed.