精神分裂症是一种病理机制复杂的疾病,受多个基因的影响。其发病机制的研究以多巴胺假说为主,以及其他假设,如5-羟色胺假设,谷氨酸假说,免疫炎症假说,基因表达异常假说,神经发育异常假说.第一代抗精神病药物是基于多巴胺能受体拮抗作用开发的,它阻断大脑中的多巴胺D2受体以发挥抗精神病作用。第二代抗精神病药通过5-羟色胺和多巴胺受体的双重阻断起作用。从第三代抗精神病药开始,抗精神病精神分裂症的治疗靶点扩展到D2受体阻滞剂之外,以探索D2受体部分激动作用和新靶点如D3,5-HT1A的抗精神病作用,5-HT7和mGlu2/3受体。第二代和第三代抗精神病药物相对于第一代抗精神病药物的主要优点是减少副作用和改善阴性症状,尽管第三代抗精神病药不能直接阻断D2受体,多巴胺递质系统的调节仍然是他们抗精神病过程的重要组成部分。根据最近的研究,几个受体,包括5-羟色胺,谷氨酸,γ-氨基丁酸,乙酰胆碱受体和去甲肾上腺素,在精神分裂症的发展中发挥作用。因此,开发新的抗精神病药物的重点已转向激动或抑制这些受体。具体来说,NMDARs兴奋剂的发展,GABA受体激动剂,mGlu受体调节剂,胆碱能受体调节剂,5-HT2C受体激动剂和α-2受体调节剂已成为主要方向。动物实验证实了这些药物的抗精神病作用,但其药代动力学和临床适用性仍需进一步探索。抗精神病药物替代靶点的研究,除了多巴胺D2受体,扩大了精神分裂症的潜在治疗选择,并为解决难治性精神分裂症的挑战提供了重要途径。本文旨在对精神分裂症的治疗靶点和用药研究进行全面综述,为该领域的治疗和进一步研究提供有价值的见解。
Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.