Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University Medical Center, 1601 23rd Ave., Nashville, TN, 37212, USA.
Functional Neuroimaging Laboratory, School of Psychology, University of Newcastle, Newcastle, Australia.
Curr Psychiatry Rep. 2018 Mar 5;20(2):10. doi: 10.1007/s11920-018-0871-5.
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.
本文综述了老年精神病学药物研发的最新进展。中枢神经系统疾病的药物研发是一个漫长而具有挑战性的过程,从临床前阶段到化合物上市,淘汰率很高。由于症状的复杂性、合并诊断和人群的可变性,开发治疗老年神经精神疾病的药物带来了额外的挑战。尽管在过去的二十年里取得的成功有限,但一些新的方法已经确定了临床前开发和最终临床测试的潜在靶点。
最近的方法试图解决与疾病进展相关的特定机制。这些方法包括将多种配体组合成多靶化合物,或针对特定类型的细胞,如蛋白激酶或髓样细胞。此外,诱导多能干细胞培养的广泛应用使得能够在特定疾病组织上测试新化合物,从而提高先导化合物通过临床前阶段的成功率。设计具有先进筛选技术和向系统药理学转变的新型药理学药物正在改变老年精神病学药物发现的格局。这些新药物有可能在长期以来无法治疗的疾病框架内产生靶向作用。