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基于磷酸二酯酶4的抑郁症治疗新靶点研究进展 被引量：3

A potential novel antidepressant target based on phosphodiesterase 4:research advances
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摘要 抑郁症是发病率最高的应激性情感障碍疾病,其机制迄今未彻底阐明,脑内单胺类神经递质缺乏、下丘脑-垂体-肾上腺轴负反馈失调、神经营养与可塑性低下等因素与抑郁症的发生密切相关。磷酸二酯酶4(phosphodiesterase 4,PDE4)是第二信使cAMP特异性水解酶,其亚型非选择性抑制剂咯利普兰(rolipram)可特异性增强cAMP信号通路,促进神经营养和可塑性,咯利普兰的抗抑郁和促认知作用及其强效、快速起效的特点也已得到证实,但由于其存在恶心、呕吐副作用,而使其终止于临床试验阶段。从PDE4中发掘介导其生物学效应而又避免副作用的关键亚型和剪接变体是该领域新药研发的关键方向。本文将主要围绕PDE4亚型及其长型剪接变体分子结构特征及其发挥抗抑郁、促认知的主要机制予以综述,为突破靶标研究的瓶颈和特色非单胺能新药的研发提供理论依据。 Depression is a prevalent and life-threatening mental disorder. Its mechanisms remain unclear. It was found that depressive disorders are closely related to monoamine neurotransmitters absence, down-regulation of hypothalamie-pituitary-adrenal （HPA） axis and neurotrophic factors and dendritic complexity in brain. Phosphodiesterase 4 （PDE4） inhibitor rolipram produce antide- pressant and memory-enhancing effects via intraeellular cAMP signaling. However, its clinical utility is limited by the major side effect of emesis, which appears to be PDE4 isoform-specific. Therefore, this research is to investigate whether long-form PDE4D variants me- diate antidepressant and cognition-enhancing effects, without causing emesis. This review summaries the PDE4 molecular structure, distribution and its antidepressant function , so as to illustrate the advantage of selective subtype inhibitor in the treatment of depres-
作者 杨卫星 王真真 龚晓健 李云峰
机构地区 中国药科大学药理教研室 军事医学科学院毒物药物研究所新药评价实验室 中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室
出处 《国际药学研究杂志》 CAS CSCD 2014年第3期291-295,共5页 Journal of International Pharmaceutical Research
基金 国家自然科学基金青年项目(81202507) 国家自然科学基金面上项目(81072624)
关键词 磷酸二酯酶4 咯利普兰 环磷酸腺苷 抑郁症 phosphodiesterase 4 （PDE4） rolipram cAMP depression
分类号 R964 [医药卫生—药理学]
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参考文献37

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二级参考文献14

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共引文献46

同被引文献32

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国际药学研究杂志
2014年 第3期

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