Tsai Guochuan E, Yang Pinchen, Chang Yue-Cune, Chong Mian-Yoon
Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
Biol Psychiatry. 2006 Feb 1;59(3):230-4. doi: 10.1016/j.biopsych.2005.06.032. Epub 2005 Sep 9.
Hypofunction of the N-methyl-d-aspartate (NMDA) subtype glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine, glycine, endogenous full agonists of the glycine site of the NMDA receptor (NMDA-glycine site), D-cycloserine, a partial agonist, or sarcosine, a glycine transporter-1 inhibitor, improves the symptoms of schizophrenia. D-alanine is another endogenous agonist of the NMDA-glycine site that might have beneficial effects on schizophrenia.
Thirty-two schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-alanine (100 mg/kg/day), which was added to their stable antipsychotic regimens. Measures of clinical efficacy and side effects were determined every other week.
Patint who received D-alanine treatment revealed significant reductions in their Clinical Global Impression Scale and Positive and Negative Syndrome Scale (PANSS) total scores. The Scale for the Assessment of Negative Symptoms and PANSS subscores of positive and cognitive symptoms were improved. D-alanine was well tolerated, and no significant side effect was noted.
The significant improvement with the D-alanine further supports the hypothesis of hypofunction of NMDA neurotransmission in schizophrenia and strengthens the proof of the principle that NMDA-enhancing treatment is a promising approach for the pharmacotherapy of schizophrenia.
N-甲基-D-天冬氨酸（NMDA）亚型谷氨酸受体功能减退与精神分裂症的病理生理学有关。用D-丝氨酸、甘氨酸（NMDA受体甘氨酸位点的内源性完全激动剂）、D-环丝氨酸（一种部分激动剂）或肌氨酸（一种甘氨酸转运体-1抑制剂）进行治疗可改善精神分裂症症状。D-丙氨酸是NMDA甘氨酸位点的另一种内源性激动剂，可能对精神分裂症有有益作用。
32名精神分裂症患者参加了一项为期6周的D-丙氨酸双盲、安慰剂对照试验（100mg/kg/天），该药物被添加到他们稳定的抗精神病治疗方案中。每隔一周测定临床疗效和副作用指标。
接受D-丙氨酸治疗的患者在临床总体印象量表和阳性与阴性症状量表（PANSS）总分上有显著降低。阴性症状评估量表以及阳性和认知症状的PANSS子量表有所改善。D-丙氨酸耐受性良好，未观察到明显副作用。
D-丙氨酸带来的显著改善进一步支持了精神分裂症中NMDA神经传递功能减退的假说，并强化了增强NMDA治疗是精神分裂症药物治疗的一种有前景方法的原理证明。
