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氯胺酮的临床作用与机制研究进展
  • ISSN号:0023-074X
  • 期刊名称:《科学通报》
  • 时间:0
  • 分类:S852.42[农业科学—基础兽医学;农业科学—兽医学;农业科学—畜牧兽医]
  • 作者机构:[1]北京大学基础医学院神经生物学系,北京大学神经科学研究所,教育部/国家卫生和计划生育委员会重点实验室,北京100191, [2]北京大学麦戈文脑研究所,北京100871
  • 相关基金:国家自然科学基金(31530028,30925015)和国家重点基础研究发展计划(2014CB542204)资助
中文摘要:

氯胺酮是常用的静脉麻醉剂之一,临床应用已超过50年.近年来,针对氯胺酮的药理作用研究取得了多方面的进展.本文从氯胺酮的麻醉作用、镇痛作用、快速抗抑郁作用和副作用等方面简要介绍其临床作用与机制研究的进展.这些进展将从剂量依赖性和靶点广泛性的角度提示一般麻醉剂发挥作用的复杂性.

英文摘要:

Ketamine is primarily known as an effective NMDAR (N-methyl-D-aspartic acid receptor) blocker. As one of the intravenous anesthetics, ketamine has been widely used in clinical practice for more than 50 years, exhibiting several different outcomes besides the original anesthetic effects. Recent studies provide insights into the mechanisms of the following neuropharmacological effects of ketamine: ( i ) Anesthesia. The anesthetic effects of ketamine are mainly due to its ability to decrease the inter-cortical communications to generate dissociative anesthesia. Besides the well-known NMDAR, another target for ketamine to show anesthetic effects has been reported to be hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels). (ii) Analgesia. Ketamine not only exhibits blockade on NMDAR in the central nervous system, but also reverses opioid tolerance when combined with morphine at a low dose. The affinity with sodium and potassium channels makes ketamine possible for analgesia at high doses. However, the clinical analgesic effect is currently controversial, and the algetic cases after the discontinuation of ketamine are probably caused by its metabolic product norketamine. (iii) Anti-depression. Ketamine is recently regarded as a rapid antidepressant drug for its contribution to neurogenesis through several molecular processes, such as the glutamate burst by activating presynaptic NMDAR and AMPAR (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor), the synaptic protein synthesis and transportation by activating mTOR (mechanistic target of rapamycin), and the synaptic maturation by releasing BDNF (brain derived neurotrophic factor). At the circuit level, ketamine widely reconstructs circuits by dual regulation on NMDAR and AMPAR, and causes loss of phenotype of the PV GABAergic neurons (parvalbumin-positive interneurons). (iv) Side effects. Ketamine is strictly constrained for its psychiatric side effects resulted from the potent disruption on n

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期刊信息
  • 《科学通报》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学院
  • 主办单位:中国科学院
  • 主编:周光召
  • 地址:北京东黄城根北街16号
  • 邮编:100717
  • 邮箱:csb@scichina.org
  • 电话:010-64036120 64012686
  • 国际标准刊号:ISSN:0023-074X
  • 国内统一刊号:ISSN:11-1784/N
  • 邮发代号:80-213
  • 获奖情况:
  • 首届国家期刊奖,中国期刊方阵“双高”期刊,第三届中国出版政府奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),美国数学评论(网络版),美国工程索引,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:81792