CEREBROSPINAL-FLUID AND SERUM CONCENTRATIONS OF THE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ANTAGONIST MEMANTINE IN MAN
CEREBROSPINAL-FLUID AND SERUM CONCENTRATIONS OF THE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ANTAGONIST MEMANTINE IN MAN
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DOI：
10.1016/0304-3940(95)11785-u
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发表时间：
1995-08-04
影响因子：
2.5
通讯作者：
QUACK, G
中科院分区：
文献类型：
--
作者：
KORNHUBER, J;QUACK, G
美金刚是一种非竞争性的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，在痴呆、痉挛和帕金森病中具有治疗潜力。在人额叶皮层中，美金刚在NMDA受体的苯环利定（PCP）结合位点处的Ki值为0.5 μ M。我们研究了在治疗条件下，脑脊液（CSF）和血清样品中的美金刚浓度是否在其在PCP结合位点处的Ki值的范围内。血清水平范围为0.025至0.529 μ M，每日剂量为5至30 mg。CSF水平与血清水平高度相关，并且每例患者的CSF水平均低于血清水平，平均CSF/血清比为0.52。血清和CSF水平与每日剂量相关，但与治疗持续时间无关。在这里报道的浓度下，美金刚预计会与NMDA受体的PCP结合位点特异性相互作用。
Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with therapeutic potential in dementia, spasticity and Parkinson's disease. The K-i-value of memantine at the phencyclidine (PCP) binding site of the NMDA receptor is 0.5 mu M in human frontal cortex, We investigated whether concentrations of memantine in cerebrospinal fluid (CSF) and serum samples under therapeutic conditions are in the range of its K-i-value at the PCP binding site. The serum levels ranged from 0.025 to 0.529 mu M with daily doses between 5 and 30 mg. CSF levels were highly correlated to serum levels and were below serum levels in each patient with a mean CSF/serum ratio of 0.52. Serum and CSF levels were correlated to the daily dose, but not to the duration of treatment. At the concentrations reported here, memantine is expected to specifically interact with the PCP binding site of the NMDA receptor.