CENTRAL-NERVOUS-SYSTEM EFFECTS OF SUBDISSOCIATIVE DOSES OF (S)-KETAMINE ARE RELATED TO PLASMA AND BRAIN CONCENTRATIONS MEASURED WITH POSITRON EMISSION TOMOGRAPHY IN HEALTHY-VOLUNTEERS
CENTRAL-NERVOUS-SYSTEM EFFECTS OF SUBDISSOCIATIVE DOSES OF (S)-KETAMINE ARE RELATED TO PLASMA AND BRAIN CONCENTRATIONS MEASURED WITH POSITRON EMISSION TOMOGRAPHY IN HEALTHY-VOLUNTEERS
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DOI：
10.1016/0009-9236(95)90194-9
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发表时间：
1995-08-01
影响因子：
6.7
通讯作者：
LANGSTROM, B
中科院分区：
文献类型：
--
作者：
HARTVIG, P;VALTYSSON, J;LANGSTROM, B
采用随机、双盲、交叉研究方法，对5名受试者注射0、0.1、0.2 mg/kg剂量(S)-氯胺酮后的血药浓度、脑内最大局部浓度和脑内特异性局部结合进行了测定，并与镇痛、健忘和情绪变化等诱导效应有关。同时给予(S)-[N-甲基-C-11]氯胺酮，正电子发射断层扫描定量测定脑组织中的特异性结合。脑内的高放射性与N-甲基-D-天冬氨酸受体复合体的区域分布相对应。由于(S)-[N-甲基-C-11]氯胺酮的置换，结合作用显著降低，且呈剂量依赖性。记忆障碍和拟精神病作用与给药剂量、给药后4min的血药浓度和脑组织中S-氯胺酮的局部结合减少有关，且在血药浓度和脑(S)-氯胺酮的最大局部浓度分别高于70和500 ng/ml时持续存在。用正电子发射断层扫描技术测量的(S)-氯胺酮的特异性结合的大小可以直接与药物作用有关。
Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-C-11]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N-methyl-D-aspartate receptor complexes. A significant and dose-dependent reduction of binding was measured as a result of displacement of (S)-[N-methyl-C-11]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.