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抗精神病药物诱发脑低温和类昏睡状态:应用前景

Antipsychotic inductors of brain hypothermia and torpor-like states: perspectives of application.

作者信息

Tarahovsky Yury S, Fadeeva Irina S, Komelina Natalia P, Khrenov Maxim O, Zakharova Nadezhda M

机构信息

Institute of Cell Biophysics RAS, Pushchino, Moscow Region, Russian Federation, 142290.

Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region, Russian Federation, 142290.

出版信息

Psychopharmacology (Berl). 2017 Jan;234(2):173-184. doi: 10.1007/s00213-016-4496-2. Epub 2016 Dec 8.

DOI:10.1007/s00213-016-4496-2
PMID:27933367
Abstract

Hypothermia and hypometabolism (hypometabothermia) normally observed during natural hibernation and torpor, allow animals to protect their body and brain against the damaging effects of adverse environment. A similar state of hypothermia can be achieved under artificial conditions through physical cooling or pharmacological effects directed at suppression of metabolism and the processes of thermoregulation. In these conditions called torpor-like states, the mammalian ability to recover from stroke, heart attack, and traumatic injuries greatly increases. Therefore, the development of therapeutic methods for different pathologies is a matter of great concern. With the discovery of the antipsychotic drug chlorpromazine in the 1950s of the last century, the first attempts to create a pharmacologically induced state of hibernation for therapeutic purposes were made. That was the beginning of numerous studies in animals and the broad use of therapeutic hypothermia in medicine. Over the last years, many new agents have been discovered which were capable of lowering the body temperature and inhibiting the metabolism. The psychotropic agents occupy a significant place among them, which, in our opinion, is not sufficiently recognized in the contemporary literature. In this review, we summarized the latest achievements related to the ability of modern antipsychotics to target specific receptors in the brain, responsible for the initiation of hypometabothermia.

摘要

在自然冬眠和蛰伏期间通常观察到的体温过低和代谢减缓(低温代谢),使动物能够保护其身体和大脑免受恶劣环境的破坏作用。在人工条件下,通过物理降温或针对抑制新陈代谢和体温调节过程的药理作用,也可以实现类似的体温过低状态。在这些被称为类蛰伏状态的条件下,哺乳动物从中风、心脏病发作和创伤性损伤中恢复的能力会大大增强。因此,针对不同病症开发治疗方法是一个备受关注的问题。随着上世纪50年代抗精神病药物氯丙嗪的发现,人们首次尝试为治疗目的创造一种药物诱导的冬眠状态。这是在动物身上进行大量研究以及在医学上广泛使用治疗性低温的开端。在过去几年中,已经发现了许多能够降低体温并抑制新陈代谢的新药物。其中,精神药物占据了重要地位,我们认为,当代文献对这一点的认识还不够充分。在这篇综述中,我们总结了与现代抗精神病药物靶向大脑中负责启动低温代谢的特定受体的能力相关的最新研究成果。

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本文引用的文献

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FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase.多巴胺能神经元中的FoxO1调节能量平衡并作用于酪氨酸羟化酶。
Nat Commun. 2016 Sep 29;7:12733. doi: 10.1038/ncomms12733.
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治疗性低温对小鼠缺血性中风后炎症细胞因子、小胶质细胞极化、迁移及功能恢复的调节作用
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