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神经活性甾体在记忆、酒精及应激相关功能方面的构效关系研究:内源性水平分析的一项关键益处

Structure-activity relationship studies on neuroactive steroids in memory, alcohol and stress-related functions: a crucial benefit from endogenous level analysis.

作者信息

Vallée Monique

机构信息

INSERM U862, Neurocentre Magendie, Pathophysiology of Addiction, Bordeaux, 33077, France,

出版信息

Psychopharmacology (Berl). 2014 Sep;231(17):3243-55. doi: 10.1007/s00213-014-3593-3. Epub 2014 Apr 30.

Abstract

RATIONALE

New research findings in the field of neuroactive steroids strongly suggest that to understand their role in physiopathology, it is essential to accurately measure their tissue levels. Through his broad chemical expertise and extensive knowledge of steroids, Dr. Robert H. Purdy pioneered structure-activity relationship studies on these compounds and developed innovative detection assays that are essential to assess their function in biological tissues.

OBJECTIVE

The goal of the present paper is to point out the specific contributions of Dr. Purdy and his collaborators to the current knowledge on the role of neuroactive steroids in the modulation of memory and alcohol- and stress-related effects with particular emphasis on the detection assays he developed to assess their endogenous levels. Reviewed here are the major results as well as the original and valuable methodological strategies issued by the long-term collaboration between Dr Purdy and many scientists worldwide on the investigation of the structure-activity relationship of neuroactive steroids.

RESULTS

Altogether, the data presented herein put forward the original notion that knowledge of the chemical structure of steroids is essential for their detection and the understanding of their role in physiological and pathological conditions, including the stress response.

CONCLUSIONS

The current challenge is to identify and quantify using appropriate methods neuroactive steroids in the context of both animal and clinical studies in order to reveal how their levels change under physiological and disease states. Dr. Purdy passed away in September 2012, but scientists all over the world will always be grateful for his pioneering work on steroid chemistry and for his great enthusiasm in research.

摘要

理论依据

神经活性甾体领域的新研究结果有力地表明,要了解它们在生理病理学中的作用,准确测量其组织水平至关重要。罗伯特·H·珀迪博士凭借其广泛的化学专业知识和对甾体的深入了解,率先开展了这些化合物的构效关系研究,并开发了创新的检测方法,这些方法对于评估它们在生物组织中的功能至关重要。

目的

本文的目的是指出珀迪博士及其合作者对当前关于神经活性甾体在记忆调节以及与酒精和应激相关效应方面作用的认识所做出的具体贡献,特别强调他为评估其内源水平而开发的检测方法。本文回顾了珀迪博士与全球众多科学家在神经活性甾体构效关系研究方面长期合作所取得的主要成果以及原始且有价值的方法策略。

结果

总体而言,本文所呈现的数据提出了一个原创观点,即甾体化学结构的知识对于其检测以及理解它们在生理和病理状况(包括应激反应)中的作用至关重要。

结论

当前的挑战是在动物和临床研究中使用适当的方法识别和量化神经活性甾体,以揭示它们在生理和疾病状态下水平如何变化。珀迪博士于2012年9月去世,但世界各地的科学家将永远感激他在甾体化学方面的开创性工作以及他对研究的极大热情。

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