Purpose of Review

While ketamine’s analgesia has mostly been attributed to antagonism of N-methyl-d-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine’s role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine’s neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented.

Recent Findings

Ketamine’s metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing.

Summary

While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine’s neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.

中文翻译：

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过去、现在和未来的氯胺酮：机制、代谢物和毒性

审查目的

虽然氯胺酮的镇痛大多归因于N-甲基拮抗d -天冬氨酸受体，有证据表明其他多种途径参与其抗抑郁和可能的镇痛作用。讨论了这些机制和氯胺酮在伤害性疼痛范式中的作用。证明氯胺酮神经毒性的动物研究尚不清楚人类可翻译性，并介绍了主要啮齿动物和人类研究的结果。

最近的发现

氯胺酮的代谢物，尤其是 (2R,6R)-羟基去甲氯胺酮，在其临床活性中的作用可能比以前认为的更大。氯胺酮对 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 的活化和雷帕霉素的哺乳动物靶标是仍在阐明的机制。氯胺酮可能在伤害性疼痛中效果最好，这涉及改变的疼痛处理。

概括

虽然对氯胺酮了解很多，但新的研究将继续确定其在临床医学中的作用。缺乏支持氯胺酮对人类神经毒性的证据，不应妨碍未来的氯胺酮临床试验。