van Berckel B N, Lipsch C, Gispen-de Wied C, Wynne H J, Blankenstein M A, van Ree J M, Kahn R S
University Hospital Utrecht Department of Psychiatry, The Netherlands.
Psychopharmacology (Berl). 1998 Jul;138(2):190-7. doi: 10.1007/s002130050662.
D-Cycloserine, a partial agonist of the glycine recognition site of the N-methyl-D-aspartate (NMDA) receptor, may serve as a probe for human cerebral NMDA receptor function. Since NMDA receptors are involved in neuroendocrine secretion, changes in pituitary secretion in response to D-cycloserine administration could serve as a model for NMDA receptor activity. The effects of an oral dose of 500 mg D-cycloserine were assessed in a neuroendocrine challenge paradigm in 20 healthy male volunteers, using a double-blind, randomized placebo-controlled crossover design. Luteinizing hormone (LH) and cortisol secretion was studied, since preclinical studies indicate that these hormones increase in response to NMDA receptor stimulation. Furthermore, plasma homovanillic acid (HVA) secretion was studied, as NMDA receptors are suggested to be involved in the regulation of dopaminergic neurotransmission. D-cycloserine was readily absorbed and did not induce side-effects or changes in vital signs and mood scores. D-Cycloserine stimulated LH secretion and induced a significant rise of the area under the plasma concentration time curve of LH. D-Cycloserine did not stimulate cortisol or plasma HVA secretion. These neuroendocrine effects suggest that D-cycloserine may be used to assess human NMDA receptor function in cerebral disorders, such as schizophrenia.
D-环丝氨酸是N-甲基-D-天冬氨酸（NMDA）受体甘氨酸识别位点的部分激动剂，可作为研究人脑NMDA受体功能的探针。由于NMDA受体参与神经内分泌分泌，给予D-环丝氨酸后垂体分泌的变化可作为NMDA受体活性的模型。采用双盲、随机、安慰剂对照的交叉设计，在20名健康男性志愿者的神经内分泌激发试验范式中评估了口服500 mg D-环丝氨酸的效果。研究了促黄体生成素（LH）和皮质醇的分泌，因为临床前研究表明这些激素会随着NMDA受体刺激而增加。此外，还研究了血浆高香草酸（HVA）的分泌，因为有研究表明NMDA受体参与多巴胺能神经传递的调节。D-环丝氨酸易于吸收，且未引起副作用或生命体征及情绪评分的变化。D-环丝氨酸刺激了LH的分泌，并使LH血浆浓度时间曲线下面积显著增加。D-环丝氨酸未刺激皮质醇或血浆HVA的分泌。这些神经内分泌效应表明，D-环丝氨酸可用于评估脑部疾病（如精神分裂症）中的人类NMDA受体功能。
