Schwasinger-Schmidt Tiffany, Preskorn Sheldon H
Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS, USA.
Department of Psychiatry and Behavioral Science, University of Kansas School of Medicine-Wichita, Wichita, KS, USA.
Adv Neurobiol. 2023;30:181-193. doi: 10.1007/978-3-031-21054-9_7.
The development of medications used to treat psychiatric conditions has largely proceeded through serendipity, where a potential drug to treat mental illness is identified by chance. This approach is based on a limited understanding of the underlying pathophysiology of mental illness and brain disorders. Identification of novel neurotransmitter systems has allowed for new molecular-based approaches for drug development that identify specific receptor targets to treat a specific symptom. An example of this approach includes the development of suvorexant, which is a dual orexin receptor antagonist FDA approved in 2014 for the treatment of insomnia. This chapter will discuss challenges in psychiatric drug development; the importance of identifying discrete neurotransmitter systems that target a specific symptom, not a syndrome; the orexin pathway and targets within this pathway that can be used to modulate sleep; and a high-throughput approach to streamlining drug development.
用于治疗精神疾病的药物研发很大程度上是通过偶然发现进行的,即偶然发现一种潜在的治疗精神疾病的药物。这种方法基于对精神疾病和脑部疾病潜在病理生理学的有限理解。新型神经递质系统的发现为基于分子的新药研发方法提供了可能,这种方法可识别特定的受体靶点以治疗特定症状。这种方法的一个例子是苏沃雷生的研发,它是一种双重食欲素受体拮抗剂,于2014年获得美国食品药品监督管理局批准用于治疗失眠。本章将讨论精神科药物研发中的挑战;识别针对特定症状而非综合征的离散神经递质系统的重要性;食欲素途径及其可用于调节睡眠的靶点;以及一种简化药物研发的高通量方法。