Advances in Drug Discovery and Development in Geriatric Psychiatry.
Advances in Drug Discovery and Development in Geriatric Psychiatry.
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DOI：
10.1007/s11920-018-0871-5
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发表时间：
2018-03-05
影响因子：
6.7
通讯作者：
Newhouse, Paul A.
中科院分区：
文献类型：
--
作者：
Conley, Alexander C.;Newhouse, Paul A.
本文综述了近年来老年精神病药物的发现和开发进展。中枢神经系统疾病的药物发现是一个漫长而具有挑战性的过程，从临床前阶段到上市的化合物具有很高的损耗率。由于症状的复杂性、共病诊断和人群的可变性，开发用于老年神经精神疾病的药物提出了额外的挑战。尽管在过去的二十年中取得了有限的成功，但许多新方法已经确定了临床前开发和最终临床测试的潜在目标。最近的方法试图解决与疾病进展相关的特定机制。这些方法包括将许多配体组合成多靶化合物，或靶向特定类型的细胞，如蛋白激酶或骨髓细胞。此外，诱导多能干细胞培养物的使用增加，使新化合物能够在疾病特异性组织上进行测试，提高了先导化合物通过临床前阶段的成功率。采用先进筛选技术设计的新药物制剂和向系统药理学的转变正在改变老年精神病学药物发现的前景。这些新药物有可能在长期无法治疗的疾病框架内产生靶向作用。
This article reviews recent advances in drug discovery and development for geriatric psychiatry. Drug discovery for disorders of the central nervous system is a long and challenging process, with a high attrition rate from the preclinical stages through to marketing a compound. Developing drugs for geriatric neuropsychiatric conditions presents additional challenges, due to the complexity of the symptoms, comorbid diagnoses, and the variability of the population. Despite there being limited success over the past two decades, a number of new approaches have identified potential targets for preclinical development and ultimately clinical testing. Recent approaches have tried to address specific mechanisms that relate to the disease progression. These approaches include combining a number of ligands into to multi-target compounds, or targeting specific types of cells such as protein kinases or myeloid cells. In addition, the increased use of induced pluripotent stem cell cultures has enabled new compounds to be tested on disease-specific tissues, increasing the success rate of the lead compounds going through the preclinical stages. New pharmacological agents designed with advanced screening techniques and the shift towards systems pharmacology is changing the landscape of drug discovery in geriatric psychiatry. There is potential for these new agents to produce targeted effects in the framework of disorders that have long been untreatable.
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DOI：
10.1186/s13195-016-0199-5
发表时间：
2016-08-30
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Blain JF;Bursavich MG;Freeman EA;Hrdlicka LA;Hodgdon HE;Chen T;Costa DE;Harrison BA;Kapadnis S;Murphy DA;Nolan S;Tu Z;Tang C;Burnett DA;Patzke H;Koenig G
通讯作者：
Koenig G
影响因子：
5
作者：
Gould RW;Dencker D;Grannan M;Bubser M;Zhan X;Wess J;Xiang Z;Locuson C;Lindsley CW;Conn PJ;Jones CK
通讯作者：
Jones CK
影响因子：
4.6
作者：
Danhof, Meindert
通讯作者：
Danhof, Meindert
影响因子：
12.8
作者：
Cooper, Andrew A.;Conklin, Laren R.
通讯作者：
Conklin, Laren R.
中枢神经系统药物发现中的激酶靶标
影响因子：
4.2
作者：
Gunosewoyo, Hendra;Yu, Lifang;Kassiou, Michael
通讯作者：
Kassiou, Michael