《快速起效抗抑郁药物的研究进展.docxVIP

快速起效抗抑郁药物的研究进展201030130195 三班段月晓 手机号码天津中医药大学研究生院 天津 300073）【摘要】目前临床使用的抗抑郁药物存在起效延迟的不足,这不仅降低了病人的依从性,还增加了其自杀的危险性。因此,如何研制出高效低毒且快速起效的抗抑郁药物成为研发热点。研究表明,选择性5-HT1A、α2自身受体拮抗剂及5-HT2A受体拮抗剂可加快5-羟色胺重摄取抑制剂及去甲肾上腺素重摄取抑制剂等抗抑郁药物的起效速度。此外, 5-HT/NE双重重摄取抑制剂及5-HT/NE/DA三重重摄取抑制剂起效时间也缩短。该文将重点围绕单胺系统对抗抑郁药物起效延迟的原因及快速起效抗抑郁药物的研究进展作一综述。【关键词】抗抑郁药物;起效时间; 5-HT1A受体拮抗剂; 5-HT2A受体拮抗剂;α2受体拮抗剂;双重/三重摄取抑制剂Progress in the development of early-onset antidepressantDuan Yuexiao(Graduate school of Tianjin University of Traditional Chinese Medicine, Tianjin, 300073)Abstract: Existing antidepressants exhibit delayed onset of action, which can decrease the compliance of the patients and enhance the risk of suicide. How to produce early-onset antidepressants with higher efficacy and lower adverse reactions has become a crucial point in the research of antidepressants. It has been demonstrated that selective 5-HT1Aantagonist,α2 antagonist and 5-HT2Aantagonist can accelerate the response of classic antidepressants. Furthermore, 5-HT/NE dual reuptake inhibitor and 5-HT/NE/DA triple reuptake inhibitor can also produce early onset of action. Here, several reasons for the delayed onset of action and the progress in the development of early-onset antidepressants are reviewed.Key words: antidepressant; onset of action; 5-HT1Aantagonist; 5-HT2Aantagonist;α2antagonist; dual/triple reuptake inhibitors抑郁症(depression)属于情感性精神障碍(mood disorders),是一种以明显而持久的心境低落为主要特征的综合征,其高发病率、高复发率和高自杀率对社会造成了极大危害。世界卫生组织(WHO)预计到2020年,抑郁症将在“全球疾病负担”排名中居第二位[1]。　抑郁症的发病机制复杂,至今尚未完全阐明。单胺假说认为,脑内单胺递质如5-羟色胺(5-HT)、去甲肾上腺素(NE)功能不足是引发抑郁症的关键因素[2],但该假说无法解释抗抑郁药物起效延迟的问题。目前比较一致的观点认为,单胺水平降低引起的受体以及受体后信号转导通路的适应性变化是抑郁症发生的关键因素。与三环类抗抑郁药物(tricyclic antidepressants,TCA s)及单胺氧化酶抑制剂(monoamine oxidase inhibitors,MAO Is)等第1代抗抑郁药物相比, 5-羟色胺重摄取抑制剂(selective serotonin reuptake inhibitors,SSR Is)及去甲肾上腺素重摄取抑制剂(noradrenaline reuptakeinhibitors,NR Is)因其受体选择性高,不良反应少,已成为临床使用的主流抗抑郁药物,但其仍存在起效延迟的不足。起效延迟不仅降低抑郁症病人依从性,还增加了其自杀危险性,因此新型抗抑郁药物研发力求在加快起效速度方面有所创新和突破。本文将重点围绕单胺系统,对抗抑郁药物起效延迟的原因及解