Ketamine: A tale of two enantiomers.
Ketamine: A tale of two enantiomers.
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氯胺酮：两个对映异构体的故事。
DOI：
10.1177/0269881120959644
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Stone JM
中科院分区：
文献类型：
--
作者：
Jelen LA;Young AH;Stone JM
解离麻醉剂氯胺酮是一种非竞争性的N-甲基-D-天冬氨酸受体拮抗剂，其快速抗抑郁作用的发现可以说是过去50年来抑郁症研究中最重要的突破。氯胺酮仍然是难治性抑郁症的标签外治疗，其因素限制了广泛使用，包括其分离效应和滥用潜力。氯胺酮是一种外消旋混合物，由等量的（S）-氯胺酮和（R）-氯胺酮组成。一种（S）-氯胺酮鼻喷雾剂已在美国和欧洲开发并批准用于治疗难治性抑郁症;然而，仍然存在一些关于疗效和副作用的担忧。虽然（R）-氯胺酮是一种不如（S）-氯胺酮有效的N-甲基-D-天冬氨酸受体拮抗剂，但越来越多的临床前证据表明（R）-氯胺酮可能比（S）-氯胺酮具有更有效和更持久的抗抑郁作用，副作用更少。此外，最近的一项（R）-氯胺酮的试点试验已经证明了对难治性抑郁症患者的快速起效和持续的抗抑郁作用。目前正在进行研究，以确定氯胺酮及其组分对映体抗抑郁作用的具体细胞和分子机制，以努力开发未来无不良反应的速效抗抑郁药。在这里，我们简要回顾了氯胺酮及其对映体的抗抑郁作用的研究结果，然后考虑潜在的机制，包括N-甲基-D-天冬氨酸受体拮抗作用，γ-氨基丁酸能的中间神经元抑制，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体激活，脑源性神经营养因子和原肌球蛋白激酶B信号，雷帕霉素复合物1和细胞外信号调节激酶信号传导的哺乳动物靶点，糖原合成酶激酶-3的抑制和外侧缰破裂的抑制，以及单胺能和阿片受体系统的潜在作用。
The discovery of the rapid antidepressant effects of the dissociative anaesthetic ketamine, an uncompetitive N-Methyl-D-Aspartate receptor antagonist, is arguably the most important breakthrough in depression research in the last 50 years. Ketamine remains an off-label treatment for treatment-resistant depression with factors that limit widespread use including its dissociative effects and abuse potential. Ketamine is a racemic mixture, composed of equal amounts of (S)-ketamine and (R)-ketamine. An (S)-ketamine nasal spray has been developed and approved for use in treatment-resistant depression in the United States and Europe; however, some concerns regarding efficacy and side effects remain. Although (R)-ketamine is a less potent N-Methyl-D-Aspartate receptor antagonist than (S)-ketamine, increasing preclinical evidence suggests (R)-ketamine may have more potent and longer lasting antidepressant effects than (S)-ketamine, alongside fewer side effects. Furthermore, a recent pilot trial of (R)-ketamine has demonstrated rapid-acting and sustained antidepressant effects in individuals with treatment-resistant depression. Research is ongoing to determine the specific cellular and molecular mechanisms underlying the antidepressant actions of ketamine and its component enantiomers in an effort to develop future rapid-acting antidepressants that lack undesirable effects. Here, we briefly review findings regarding the antidepressant effects of ketamine and its enantiomers before considering underlying mechanisms including N-Methyl-D-Aspartate receptor antagonism, γ-aminobutyric acid-ergic interneuron inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor activation, brain-derived neurotrophic factor and tropomyosin kinase B signalling, mammalian target of rapamycin complex 1 and extracellular signal-regulated kinase signalling, inhibition of glycogen synthase kinase-3 and inhibition of lateral habenula bursting, alongside potential roles of the monoaminergic and opioid receptor systems.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
4.7
作者：
Buritova, Jaroslava;Berrichon, Geraldine;Cussac, Didier
通讯作者：
Cussac, Didier
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
25.8
作者：
Daly, Ella J.;Singh, Jaskaran B.;Drevets, Wayne C.
通讯作者：
Drevets, Wayne C.
DOI：
10.1124/jpet.116.235838
发表时间：
2016-10-01
影响因子：
3.5
作者：
Can, Adem;Zanos, Panos;Gould, Todd D.
通讯作者：
Gould, Todd D.