Krystal J H, Karper L P, Bennett A, D'Souza D C, Abi-Dargham A, Morrissey K, Abi-Saab D, Bremner J D, Bowers M B, Suckow R F, Stetson P, Heninger G R, Charney D S
Department of Psychiatry, Yale University School of Medicine, Connecticut, USA.
Psychopharmacology (Berl). 1998 Feb;135(3):213-29. doi: 10.1007/s002130050503.
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with psychotogenic and dissociative effects in healthy humans. These cognitive and perceptual effects in humans are reportedly reduced by benzodiazepine premedication. This study assessed the interactive effects of a ketamine (i.v. bolus of 0.26 mg/kg followed by an infusion of 0.65 mg/kg per hour) and lorazepam 2 mg., PO, in humans. Twenty-three healthy subjects completed 4 test days involving the oral administration of lorazepam or matched placebo 2 h prior to the i.v. infusion of ketamine or placebo. Ketamine: 1) produced behaviors similar to the positive and negative symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale (BPRS); 2) evoked perceptual alterations as measured by the Clinician-Administered Dissociative States Scale (CADSS); 3) impaired performance on the Wisconsin Card Sorting Test (WCST) and other tests sensitive to frontal cortical impairment; and 4) had amnestic effects. Lorazepam produced attention impairments, concrete proverb interpretations, and recall impairments. Lorazepam reduced ketamine-associated emotional distress and there was a non-significant trend for it to decrease perceptual alterations produced by ketamine. However, it failed to reduce many cognitive and behavioral effects of ketamine, including psychosis. Further, lorazepam exacerbated the sedative, attention-impairing, and amnestic effects of ketamine. There was no evidence of pharmacokinetic interaction between these medications. These data suggest that subhypnotic lorazepam and ketamine show a spectrum of interactive effects, ranging from antagonism to potentiation.
氯胺酮是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，对健康人具有致幻和分离作用。据报道，苯二氮䓬类药物预处理可减轻氯胺酮对人类的这些认知和感知影响。本研究评估了氯胺酮（静脉推注0.26mg/kg，随后每小时输注0.65mg/kg）与2mg口服劳拉西泮在人体中的相互作用。23名健康受试者完成了4个测试日，在静脉输注氯胺酮或安慰剂前2小时口服劳拉西泮或匹配的安慰剂。氯胺酮：1）产生与精神分裂症的阳性和阴性症状相似的行为，通过简明精神病评定量表（BPRS）评估；2）引起感知改变，通过临床医生实施的分离状态量表（CADSS）测量；3）损害威斯康星卡片分类测试（WCST）和其他对额叶皮质损伤敏感的测试的表现；4）具有遗忘作用。劳拉西泮产生注意力损害、具体谚语解释和回忆损害。劳拉西泮减轻了与氯胺酮相关的情绪困扰，并且有一个不显著的趋势，即它减少了氯胺酮产生的感知改变。然而，它未能减轻氯胺酮的许多认知和行为影响，包括精神病。此外，劳拉西泮加剧了氯胺酮的镇静、注意力损害和遗忘作用。没有证据表明这些药物之间存在药代动力学相互作用。这些数据表明，亚催眠剂量的劳拉西泮和氯胺酮显示出一系列相互作用，从拮抗到增强。
