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血清素:一个永无止境的故事。

Serotonin: a never-ending story.

作者信息

Olivier Berend

机构信息

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences & Brain Center Rudolf Magnus, Utrecht University, Universiteitsweg 99, 3584CG Utrecht, The Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, USA.

出版信息

Eur J Pharmacol. 2015 Apr 15;753:2-18. doi: 10.1016/j.ejphar.2014.10.031. Epub 2014 Nov 7.

Abstract

The neurotransmitter serotonin is an evolutionary ancient molecule that has remarkable modulatory effects in almost all central nervous system integrative functions, such as mood, anxiety, stress, aggression, feeding, cognition and sexual behavior. After giving a short outline of the serotonergic system (anatomy, receptors, transporter) the author's contributions over the last 40 years in the role of serotonin in depression, aggression, anxiety, stress and sexual behavior is outlined. Each area delineates the work performed on animal model development, drug discovery and development. Most of the research work described has started from an industrial perspective, aimed at developing animals models for psychiatric diseases and leading to putative new innovative psychotropic drugs, like in the cases of the SSRI fluvoxamine, the serenic eltoprazine and the anxiolytic flesinoxan. Later this research work mainly focused on developing translational animal models for psychiatric diseases and implicating them in the search for mechanisms involved in normal and diseased brains and finding new concepts for appropriate drugs.

摘要

神经递质5-羟色胺是一种进化上古老的分子,几乎在所有中枢神经系统整合功能中都具有显著的调节作用,如情绪、焦虑、应激、攻击行为、进食、认知和性行为。在简要概述5-羟色胺能系统(解剖学、受体、转运体)之后,概述了作者在过去40年里对5-羟色胺在抑郁、攻击行为、焦虑、应激和性行为中作用的贡献。每个领域都阐述了在动物模型开发、药物发现与开发方面所开展的工作。所描述的大多数研究工作都从产业角度出发,旨在开发精神疾病动物模型,并研发可能的新型创新精神药物,如选择性5-羟色胺再摄取抑制剂氟伏沙明、镇静剂依他普嗪和抗焦虑药氟辛克生的情况。后来,这项研究工作主要集中在开发精神疾病的转化动物模型,并将其用于探寻正常和患病大脑所涉及的机制,以及寻找合适药物的新概念。

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