Carfagno M L, Hoskins L A, Pinto M E, Yeh J C, Raffa R B
School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
Ann Pharmacother. 2000 Jun;34(6):788-97. doi: 10.1345/aph.19146.
To summarize the published preclinical and clinical data that suggest the possible use of glutamate receptor agonists or antagonists as novel antipsychotic agents.
Primary and review articles were identified by MEDLINE search (from 1966 to December 1999) and through secondary sources.
All of the articles identified from the data sources were evaluated and all information deemed relevant was included.
The standard antipsychotic drugs, whose clinical activity correlates with affinity for dopamine D2 receptors, alleviate some of the positive symptoms of schizophrenia, but have limited impact on negative symptoms. Several lines of evidence implicate glutamate-receptor system dysfunction(s) in schizophrenia, either as causative or contributory factors. In addition, several standard antipsychotic drugs modulate glutamate or glutamate receptor activity, suggesting an alternative view of their mechanism of antipsychotic action. Preliminary studies have shown that drugs which modulate glutamate brain concentrations have positive effects in animal models of schizophrenia.
A role for glutamate in the pathogenesis or pharmacotherapy of schizophrenia is suggested from anatomic (interactions between glutamatergic and dopaminergic systems in relevant brain regions), physiologic (implication of glutamate-receptor dysfunction), and pharmacologic (modulation of glutamate or glutamate receptors) evidence. Therefore, compounds that function at glutamate receptors might represent a novel approach to the treatment of the disease or to the amelioration of symptoms, either as monotherapy or as an adjunct to dopamine D2 receptor antagonists.
总结已发表的临床前和临床数据，这些数据提示谷氨酸受体激动剂或拮抗剂可能作为新型抗精神病药物使用。
通过MEDLINE检索（1966年至1999年12月）及二级来源确定了原始文章和综述文章。
对从数据来源中识别出的所有文章进行评估，并纳入所有被认为相关的信息。
标准抗精神病药物的临床活性与对多巴胺D2受体的亲和力相关，可缓解精神分裂症的一些阳性症状，但对阴性症状的影响有限。有几条证据表明谷氨酸受体系统功能障碍在精神分裂症中是致病因素或促成因素。此外，几种标准抗精神病药物可调节谷氨酸或谷氨酸受体活性，提示对其抗精神病作用机制的另一种观点。初步研究表明，调节谷氨酸脑浓度的药物在精神分裂症动物模型中具有积极作用。
从解剖学（相关脑区谷氨酸能和多巴胺能系统之间的相互作用）、生理学（谷氨酸受体功能障碍的影响）和药理学（谷氨酸或谷氨酸受体的调节）证据来看，谷氨酸在精神分裂症的发病机制或药物治疗中可能起作用。因此，作用于谷氨酸受体的化合物可能代表一种治疗该疾病或改善症状的新方法，可作为单一疗法或多巴胺D2受体拮抗剂的辅助疗法。
