SUBANESTHETIC EFFECTS OF THE NONCOMPETITIVE NMDA ANTAGONIST, KETAMINE, IN HUMANS - PSYCHOTOMIMETIC, PERCEPTUAL, COGNITIVE, AND NEUROENDOCRINE RESPONSES
SUBANESTHETIC EFFECTS OF THE NONCOMPETITIVE NMDA ANTAGONIST, KETAMINE, IN HUMANS - PSYCHOTOMIMETIC, PERCEPTUAL, COGNITIVE, AND NEUROENDOCRINE RESPONSES
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DOI：
10.1001/archpsyc.1994.03950030035004
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发表时间：
1994-03-01
影响因子：
--
通讯作者：
CHARNEY, DS
中科院分区：
文献类型：
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作者：
KRYSTAL, JH;KARPER, LP;CHARNEY, DS
工作背景：进一步表征亚麻醉剂量盐酸氯胺酮在健康人类受试者中的行为、认知、神经内分泌和生理效应。氯胺酮，盐酸苯环利定衍生物，是一种解离性麻醉剂和非竞争性拮抗剂的N-甲基-D-天冬氨酸亚型兴奋性氨基酸receptor.Methods：19名健康受试者招募的广告从社区参加了这项随机，双盲，安慰剂对照研究。受试者完成了三个试验日，包括40分钟的安慰剂、盐酸氯胺酮（0.1 mg/kg）或盐酸氯胺酮（0.5 mg/kg）静脉给药。采用简明精神病评定量表对精神分裂症阳性和阴性症状相关行为进行评定。通过威斯康星州精神病倾向量表的知觉偏差子量表和临床医生-管理者分离状态量表评估与分离状态相关的知觉和行为变化。认知功能评估采用（1）简易精神状态检查;（2）对额叶皮质功能障碍敏感的测试，包括连续表现警戒任务、语言流畅性任务和威斯康星州卡片分类测试;（3）即时和延迟回忆测试。结果：氯胺酮（1）引起类似精神分裂症阳性和阴性症状的行为，（2）引起知觉的改变，（3）引起警觉性、言语流畅性和威斯康星州卡片分类测试的表现受损，（4）引起类似分离状态的症状，（5）引起类似精神分裂症阴性和阳性症状的行为，（6）引起类似精神分裂症阴性和阳性症状的行为。（5）优先中断延迟词回忆，保留即时回忆和分心后回忆。在研究剂量下，氯胺酮对简易精神状态检查无显著影响。氯胺酮对血浆3-甲氧基-4-羟基苯乙二醇水平也没有影响，尽管在较高剂量下，氯胺酮使血浆高香草酸水平在试验日的下降减弱。它还剂量依赖性地增加血浆皮质醇和催乳素水平。氯胺酮产生小剂量依赖性增加血压。结论：这些数据表明，N-甲基-D-天冬氨酸拮抗剂产生广泛的症状，行为和认知缺陷，类似于内源性精神病，特别是精神分裂症和解离状态的方面。
Background: To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects. Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor.Methods: Nineteen healthy subjects recruited by advertisements from the community participated in this randomized, double-blind, placebo-controlled study. Subjects completed three test days involving the 40-minute intravenous administration of placebo, ketamine hydrochloride (0.1 mg/kg), or ketamine hydrochloride (0.5 mg/kg). Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale. Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Administered Dissociative States Scale. Cognitive function was assessed by using the (1) Mini-Mental State Examination; (2) tests sensitive to frontal cortical dysfunction, including a continuous performance vigilance task, a verbal fluency task, and the Wisconsin Card Sorting Test; and (3) tests of immediate and delayed recall. Plasma levels of cortisol, prolactin, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol were measured.Results: Ketamine (1) produced behaviors similar to the positive and negative symptoms of schizophrenia; (2) elicited alterations in perception; (3) impaired performance on tests of vigilance, verbal fluency, and the Wisconsin Card Sorting Test; (4) evoked symptoms similar to dissociative states; and (5) preferentially disrupted delayed word recall, sparing immediate recall and postdistraction recall. Ketamine had no significant effect on the Mini-Mental State Examination at the doses studied. Ketamine also had no effect on plasma 3-methoxy-4-hydroxyphenethyleneglycol levels, although it blunted a test day decline in plasma homovanillic acid levels at the higher dose. it also dose dependently increased plasma cortisol and prolactin levels. Ketamine produced small dose-dependent increases in blood pressure.Conclusions: These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.