50 years of hurdles and hope in anxiolytic drug discovery.
50 years of hurdles and hope in anxiolytic drug discovery.
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50 年来抗焦虑药物发现的障碍和希望。
DOI：
10.1038/nrd4075
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发表时间：
2013-09
期刊：
影响因子：
--
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中科院分区：
文献类型：
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作者：
焦虑症是最常见的一组精神疾病，有很高的个人和社会代价。为这些疾病寻找新的药理治疗方法是由于日益增长的医疗需求，即改善现有药物的有效性和副作用。抗焦虑药物发现研究产生了大量数据，导致许多新分子进入临床试验。然而，这些努力的临床结果一直令人失望，因为在啮齿动物研究中使用新型药物的有希望的结果很少转化为对人类的有效性。在这里，我们分析了过去50年来临床前研究的主要趋势，这些研究旨在寻找新药，而不是那些针对典型的焦虑症相关的GABA(γ-氨基丁酸)-苯二氮卓系统的药物，这些系统最集中地集中在5-羟色胺、神经肽、谷氨酸和内源性大麻系统上。我们强调了可能阻碍该领域进展的各种关键问题，并就未来如何更有效地发现抗焦虑药物提出了建议。
Anxiety disorders are the most prevalent group of psychiatric diseases, and have high personal and societal costs. The search for novel pharmacological treatments for these conditions is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. A huge volume of data has been generated by anxiolytic drug discovery studies, which has led to the progression of numerous new molecules into clinical trials. However, the clinical outcome of these efforts has been disappointing, as promising results with novel agents in rodent studies have very rarely translated into effectiveness in humans. Here, we analyse the major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (γ-aminobutyric acid)–benzodiazepine system, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems. We highlight various key issues that may have hampered progress in the field, and offer recommendations for how anxiolytic drug discovery can be more effective in the future.
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DOI：
10.1186/2045-5380-1-9
发表时间：
2011-11-07
期刊：
Biology of mood & anxiety disorders
影响因子：
--
作者：
Belzung C;Lemoine M
通讯作者：
Lemoine M
影响因子：
2
作者：
Bergado-Acosta, Jorge R.;Sangha, Susan;Stork, Oliver
通讯作者：
Stork, Oliver
影响因子：
16.2
作者：
Bielsky, IF;Hu, SB;Young, LJ
通讯作者：
Young, LJ
影响因子：
2.9
作者：
Bhatnagar, S;Sun, LM;Dallman, MF
通讯作者：
Dallman, MF
DOI：
10.1016/s1569-7339(07)00014-8
发表时间：
2008-01-01
期刊：
HANDBOOK OF ANXIETY AND FEAR
影响因子：
--
作者：
Bortolato, Marco;Piomelli, Daniele
通讯作者：
Piomelli, Daniele