Uzbay I Tayfun
Gülhane Askeri Tip Fak., Tibbi Farmakoloji AD., Ankara.
Turk Psikiyatri Derg. 2009 Summer;20(2):175-82.
Schizophrenia is a serious mental disorder with a challenging rational pharmacotherapy. Neurochemical transmission in the dopaminergic system, especially via D2 receptors, and related changes in postsynaptic signal transduction are very important in both the formation of schizophrenia and current pharmacotherapeutic treatment with antipsychotic drugs. Blocking the serotonergic 5-HT2A and 5-HT2C receptors is growing growing importance with regard to the action mechanisms of new generation antipsychotic medications. Recent preclinical and clinical data show that dysfunction of central neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurophin-3 (NT-3) might contribute to impaired brain development and neuroplasticity, leading to schizophrenia. In addition, some recent studies suggest that there is an important relationship between alcohol and substance addiction, and schizophrenia. There is also some preclinical data indicating that the central nitrergic system and agmatine(3/4)a biologically active agent produced after decarboxylation of arginine(3/4)might be interesting and important targets for understanding the etiopathogenesis of schizophrenia and for development of new drugs. Selective dopamine D3 receptor antagonists, specific agonists for metabotropic and NMDA receptors of the glutamatergic system, and nicotinic alpha-7 receptor agonists were reported in preclinical and a limited number of clinical studies as potential new targets for schizophrenia treatment. In this review, new advances in the pharmacotherapy of schizophrenia and possible new targets are discussed in the light of the current literature.
精神分裂症是一种严重的精神障碍,其合理药物治疗颇具挑战性。多巴胺能系统中的神经化学传递,尤其是通过D2受体的传递,以及突触后信号转导的相关变化,在精神分裂症的形成以及目前使用抗精神病药物的药物治疗中都非常重要。就新一代抗精神病药物的作用机制而言,阻断5-羟色胺能5-HT2A和5-HT2C受体的重要性日益凸显。最近的临床前和临床数据表明,中枢神经营养因子功能障碍,如神经生长因子(NGF)、脑源性神经营养因子(BDNF)和神经营养素-3(NT-3),可能导致大脑发育受损和神经可塑性受损,进而引发精神分裂症。此外,一些近期研究表明,酒精和物质成瘾与精神分裂症之间存在重要关联。也有一些临床前数据表明,中枢一氧化氮能系统和胍丁胺(精氨酸脱羧后产生的一种生物活性剂)可能是理解精神分裂症病因发病机制和开发新药的有趣且重要的靶点。在临床前和一些有限的临床研究中,选择性多巴胺D3受体拮抗剂、谷氨酸能系统代谢型和NMDA受体的特异性激动剂以及烟碱α-7受体激动剂被报道为精神分裂症治疗的潜在新靶点。在本综述中,将根据当前文献讨论精神分裂症药物治疗的新进展和可能的新靶点。