Cáceda Ricardo, Kinkead Becky, Nemeroff Charles B
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Semin Clin Neuropsychiatry. 2003 Apr;8(2):94-108. doi: 10.1053/scnp.2003.50009.
Schizophrenia is one of the major psychiatric disorders for which effective pharmacotherapy has been available for approximately 50 years. Study of the mechanism of action of these antipsychotic drugs (APDs) has largely focused on the mesolimbic dopamine system and in the neurotransmitter systems that regulate it. Modulation of the neurotensin (NT) circuit in the mesolimbic system can underlie the mechanism of action of APDs. Several lines of evidence support this hypothesis, including: (1) association of NT with neural circuits relevant to the pathophysiology of schizophrenia and the therapeutic effects of APDs; (2) prediction of antipsychotic efficacy and side effect liability based on APD effects on the NT system; (3) low concentrations of NT in the cerebrospinal fluid of a subset of patients with schizophrenia and its normalization after associated clinical improvement with APDs; and (4) remarkable behavioral similarities between peripherally administered APDs and central NT administration. For these reasons, drugs that directly modify the activity of NT systems, particularly NT receptor agonists, could plausibly represent a novel class of APDs.
精神分裂症是主要的精神疾病之一，大约50年来一直有有效的药物治疗方法。这些抗精神病药物（APD）作用机制的研究主要集中在中脑边缘多巴胺系统以及调节该系统的神经递质系统。中脑边缘系统中神经降压素（NT）回路的调节可能是APD作用机制的基础。几条证据支持这一假说，包括：（1）NT与精神分裂症病理生理学及APD治疗效果相关的神经回路的关联；（2）基于APD对NT系统的作用预测抗精神病疗效和副作用倾向；（3）一部分精神分裂症患者脑脊液中NT浓度较低，且在使用APD临床改善后恢复正常；（4）外周给予APD与中枢给予NT之间显著的行为相似性。基于这些原因，直接改变NT系统活性的药物，尤其是NT受体激动剂，可能代表一类新型的APD。
