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精神病学药物研发史:意外发现的一课。

The History of Drug Development in Psychiatry: A Lesson in Serendipity.

作者信息

Wadhwa Abhishek

机构信息

University of Alabama at Birmingham, Department of Psychiatry and Behavioral Neurobiology, Birmingham, AL, USA.

出版信息

Adv Neurobiol. 2023;30:19-35. doi: 10.1007/978-3-031-21054-9_2.

Abstract

The goal of this book is to provide a guide on modern day drug development in psychiatry. However, in order to understand current practices in drug development, it is important to first understand the history of psychiatry including early attempts at drug discovery and develoment. The early history of psychiatry is mired with the use of inhumane experimental treatments and the institutionalization of patients in asylums. Some of the earliest drugs used in these asylums were meant to sedate patients rather than treat underlying mental disorders. The earliest identified drugs treating mental disorders were born out of serendipitous discoveries which later led to their clinical effects being demonstrated through clinical trials and case studies. This is evident from the history of chlorpromazine, monoamine oxidase inhibitors, tricyclic antidepressants, lithium, and others. We discuss in detail about each of these psychotropic drugs, the events leading up to their discovery, and their role in formulating the biological basis of mental disorders including schizophrenia, depression, and bipolar disorder. Psychiatry, it seems has worked its way backwards from first identifying treatments before understanding the biological basis of mental disorders, in a sharp contrast to the other fields of medicine. With our growing understanding of the etiopathogenesis of mental disorders, drug development in psychiatry is evolving to develop treatments that target the underlying physiology of mental disorders.

摘要

本书的目标是提供一本关于当代精神病学药物研发的指南。然而,为了理解当前药物研发的实践,首先了解精神病学的历史很重要,包括早期药物发现与开发的尝试。精神病学的早期历史充斥着不人道的实验性治疗以及将患者收容于精神病院的做法。这些精神病院里最早使用的一些药物旨在使患者镇静,而非治疗潜在的精神障碍。最早被确定用于治疗精神障碍的药物源自偶然发现,后来通过临床试验和案例研究证实了它们的临床疗效。这从氯丙嗪、单胺氧化酶抑制剂、三环类抗抑郁药、锂盐等药物的历史中可见一斑。我们将详细讨论每一种这些精神药物、导致其发现的事件,以及它们在构建包括精神分裂症、抑郁症和双相情感障碍在内的精神障碍生物学基础方面所起的作用。精神病学似乎是在尚未理解精神障碍生物学基础之前就先确定了治疗方法,这与医学的其他领域形成了鲜明对比。随着我们对精神障碍病因发病机制的认识不断加深,精神病学的药物研发正在不断演进,以开发针对精神障碍潜在生理机制的治疗方法。

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