解毒剂:起源、药物发现和机制。

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES
Jeffrey M. Witkin , James E. Barrett
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引用次数: 0

摘要

焦虑是人类生存条件的一部分,几个世纪以来,人们一直在使用精神活性物质来控制焦虑。目前,抗焦虑药物的医疗需求和社会需求并未减少。本概述简要介绍了现代抗焦虑药物(包括苯二氮卓类药物)的发现历史,并讨论了对新型抗焦虑药物的持续医疗需求。本文还讨论了行为药理学在抗焦虑药临床前开发中的应用和影响。综述随后强调了通过 GABAA 受体增效和阻断单胺摄取以外的机制来开发新一代抗焦虑药的机制多样性。随后讨论了抗焦虑药的行为特异性作用,包括开发抗焦虑选择性药物的概念,这种药物既能针对焦虑,又不会产生包括镇静和依赖性在内的不良反应。此外,还简要回顾了抗焦虑药在治疗药物使用障碍等其他疾病方面的应用。最后,简要概述了抗焦虑药物的研发现状。综述最后认为,尽管抗焦虑药物种类繁多,但由于某些药物对某些患者缺乏疗效,且存在副作用和安全性问题,因此需要有替代药物。目前的临床前和临床研究正在进行中,目标是找出此类化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ANXIOLYTICS: Origins, drug discovery, and mechanisms

Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxiolytics through mechanisms beyond the potentiation of GABAA receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.

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来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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