快速起效抗抑郁药物研究进展  

Advances in fast onset antidepressants

作　　者：黄吉生[1,2] 杜金平[1,2] 徐砚通[1,2] 

机构地区：[1]天津中医药大学天津市现代中药重点实验室,天津300193 [2]天津国际生物医药联合研究院中药新药研发中心,天津300457

出　　处：《中国新药杂志》2015年第23期2669-2676,共8页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2012ZX09304007;2013ZX09201020);科技部国家国际合作专项(2013DFA31620);天津市应用基础及前沿技术研究计划项目(12JCYBJC32400)

摘　　要：临床起效缓慢是目前抗抑郁药物治疗的明显不足,因此迫切需要快速起效抗抑郁药物。基于已报道抗抑郁药物作用特点,根据起效时间分为快、中、慢速三类:快速特指数小时内起效,如NMDA受体拮抗剂;中速特指7 d内起效,包括乙酰胆碱M受体拮抗剂、5-HT_(2c)受体拮抗剂、5-HT_4受体激动剂、5-HT_7受体拮抗剂、ATP和乙酰左旋肉毒碱等;慢速特指14 d以上起效,包括传统单胺转运体抑制剂和单胺氧化酶抑制剂。根据抗抑郁药物作用机制,提出了抗抑郁行为改变的启动扳机假说解释药物起效快慢现象。快速起效抗抑郁药物研究拓展了单胺类神经递质系统为靶点的传统框架,为研发抗抑郁新药和揭示抑郁症病理生理机制提供了重要参考。Delayed onset of clinical effects is a major drawback for traditional antidepressants,so it is an urgent need to develop fast onset antidepressants. According to the antidepressant actions reported so far,antidepressants can be categorized into three groups： the fast onset group takes effects within hours,such as antiagonists of NMDA receptor; the middle onset group takes effects within less than 7 days,including antagonists of muscarinic receptor,antagonists of 5-HT_2 creceptor,agonists of 5-HT_4 receptor,antagonists of 5-HT_7 receptor,ATP and L-acetylcarnitine; the slow onset group takes effects by longer than 14 days,including inhibitors of monoamine transporters and inhibitors of monoamine oxidase. Based on the known antidepressant mechanisms,a hypothesis on trigger of behavioral changes in anti-depression was proposed to explain the different onset time of antidepressants. The studies on fast onset antidepressants expand the frame of traditional targets on monoamine neurotransmitter system and provide critical information for both drug discovery and pathophysiology of depression.

关 键 词：抗抑郁 快速起效 药物靶点和机制 

分 类 号：R964[医药卫生—药理学]