Semba J
University of the Air, Division of Health Sciences, Chiba, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1998 Jun;18(3):71-80.
A major ground of dopamine hypothesis of schizophrenia is that all antipsychotics share dopamine D2 antagonistic activity. However, they are less effective in ameliorating the negative symptoms of schizophrenia. Recently, glutamate hypothesis of schizophrenia has been developed from the observation that phencyclidine, an NMDA receptor antagonist, induces a psychotic state closely resembling schizophrenia in normal individuals. Because glycine potentiates NMDA receptor activity, it has been tried as an adjunct to conventional antipsychotics. Most trials demonstrated a moderate improvement in negative symptoms. In this review we discussed the clinical usefulness of glycine therapy. First we described glutamate hypothesis of schizophrenia as a theoretical basis of glycine therapy. Then we reviewed clinical trials of glycine or other glycinergic agents (glycine receptor partial agonist, D-cycloserine, or the glycine prodrug milacemide). Although long-term side effects of glycine administration have not been fully investigated, glycine therapy could be a potential therapeutic tool for the negative symptoms of schizophrenia.
精神分裂症多巴胺假说的一个主要依据是，所有抗精神病药物都具有多巴胺D2拮抗活性。然而，它们在改善精神分裂症阴性症状方面效果较差。最近，精神分裂症的谷氨酸假说源于这样的观察：N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环利定可在正常个体中诱发与精神分裂症极为相似的精神病状态。由于甘氨酸可增强NMDA受体活性，它已被尝试作为传统抗精神病药物的辅助用药。大多数试验表明，阴性症状有适度改善。在本综述中，我们讨论了甘氨酸治疗的临床实用性。首先，我们将精神分裂症的谷氨酸假说描述为甘氨酸治疗的理论基础。然后，我们回顾了甘氨酸或其他甘氨酸能药物（甘氨酸受体部分激动剂、D-环丝氨酸或甘氨酸前药米拉醋胺）的临床试验。尽管尚未充分研究甘氨酸给药的长期副作用，但甘氨酸治疗可能是治疗精神分裂症阴性症状的一种潜在治疗手段。
