Heresco-Levy U, Silipo G, Javitt D C
Department of Psychiatry, Hadassah Medical School, Sarah Herzog Memorial Hospital, Jerusalem, Israel.
Psychopharmacol Bull. 1996;32(4):731-40.
Phencyclidine (PCP) induces a psychotic state closely resembling schizophrenia in normal individuals. PCP and related agents induce their unique behavioral effects by blocking neurotransmission mediated at N-methyl-D-aspartate (NMDA)-type glutamate receptors, indicating that dysfunction of NMDA receptor-mediated neurotransmission may play a crucial role in the pathophysiology of schizophrenia. NMDA receptors are activated by the amino acids glutamate and glycine, working at independent binding sites. Glutamate cannot be administered exogenously because of excitotoxicity. In contrast, glycine administered exogenously may potentiate NMDA receptor-mediated neurotransmission in vivo following peripheral administration. In rodents, glycine is effective in elevating brain glycine levels and reversing PCP-induced hyperactivity at doses of 0.8 g/kg and above. Three studies have now been completed utilizing moderate to high (0.4-0.8 g/kg/day) doses of glycine, added to neuroleptics, for the treatment of schizophrenia. Across studies, 15 to 30 percent improvement in negative symptoms was observed with no corresponding worsening of positive symptoms. Although preliminary, these studies indicate that dietary supplementation with glycine or treatment with other glycinergic agents may be effective in the treatment of schizophrenia.
苯环己哌啶（PCP）可使正常个体产生与精神分裂症极为相似的精神病状态。PCP及相关药物通过阻断N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体介导的神经传递来产生其独特的行为效应，这表明NMDA受体介导的神经传递功能障碍可能在精神分裂症的病理生理学中起关键作用。NMDA受体由氨基酸谷氨酸和甘氨酸激活，它们作用于独立的结合位点。由于存在兴奋性毒性，谷氨酸不能通过外源性给药。相比之下，外周给药后，外源性给予甘氨酸可能会增强体内NMDA受体介导的神经传递。在啮齿动物中，甘氨酸在剂量为0.8 g/kg及以上时，可有效提高脑内甘氨酸水平并逆转PCP诱导的多动。目前已经完成了三项研究，将中等至高剂量（0.4 - 0.8 g/kg/天）的甘氨酸添加到抗精神病药物中用于治疗精神分裂症。在各项研究中，观察到阴性症状有15%至30%的改善，而阳性症状没有相应恶化。尽管这些研究尚属初步，但表明饮食中补充甘氨酸或使用其他甘氨酸能药物进行治疗可能对精神分裂症有效。
