Attenuation of the neuropsychiatric effects of ketamine with lamotrigine -: Support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists
Attenuation of the neuropsychiatric effects of ketamine with lamotrigine -: Support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists
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DOI：
10.1001/archpsyc.57.3.270
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发表时间：
2000-03-01
影响因子：
--
通讯作者：
Krystal, JH
中科院分区：
文献类型：
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作者：
Anand, A;Charney, DS;Krystal, JH
背景资料：N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，如苯环己哌啶和氯胺酮的认知，行为和情绪的影响，已被用来研究NMDA受体功能障碍的影响。NMDA受体拮抗剂，如氯胺酮的作用的药理学调节，可能会导致精神疾病，如精神分裂症的新的治疗药物的发展。临床前研究表明，氯胺酮的一些作用可能是通过增加谷氨酸释放介导的。在这项研究中，我们测试了拉莫三嗪，一种抑制谷氨酸释放的药物，将减少氯胺酮对人类神经精神影响的假设。方法：健康受试者（n = 16）完成了4个试验日，包括口服拉莫三嗪300 mg，或安慰剂，在双盲条件下以随机顺序给予氯胺酮（静脉推注0.26 mg/kg和静脉输注0.65 mg/kg/小时）或安慰剂前2小时。结果：拉莫三嗪能显著降低氯胺酮引起的知觉异常（由临床医师评估）;管理者分离状态量表（P
Background: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans.Method: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications.Results: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician;Administered Dissociative States Scale (P