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抗精神病药引起代谢副作用的临床前模型。

Preclinical models of antipsychotic drug-induced metabolic side effects.

机构信息

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, B.C., Canada, V6T 1Z3.

出版信息

Trends Pharmacol Sci. 2010 Oct;31(10):484-97. doi: 10.1016/j.tips.2010.07.002. Epub 2010 Aug 2.

Abstract

Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biology of APD-induced side effects in humans is poorly understood, and therefore preclinical rodent models are essential for translational research. With numerous recent studies on the topic, there is an emerging consensus that some symptoms, such as glucose dysregulation and insulin resistance, are more reliably observed than others, such as weight gain and hypertension, but, comparison between preclinical studies is complicated by numerous factors, including drug-specific effects and variables such as diet and treatment regimen. In this paper, we provide a major review of this important and growing field of preclinical study, and address crucial issues for future research.

摘要

抗精神病药物(APDs),尤其是“非典型”APD,通常与人类的代谢副作用有关。这些副作用包括葡萄糖调节不良、胰岛素抵抗、血脂异常、体重增加和高血压,使患者患心血管代谢疾病的风险增加。人类 APD 诱导的副作用的潜在生物学机制理解得很差,因此临床前啮齿动物模型对于转化研究至关重要。由于最近有许多关于这个主题的研究,人们越来越达成共识,即一些症状,如葡萄糖调节不良和胰岛素抵抗,比其他症状(如体重增加和高血压)更可靠地观察到,但由于药物特异性效应和饮食、治疗方案等变量等诸多因素,临床前研究之间的比较变得复杂。在本文中,我们对这一重要且不断发展的临床前研究领域进行了全面回顾,并解决了未来研究的关键问题。

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