Current approaches for the discovery of drugs that deter substance and drug abuse.
Current approaches for the discovery of drugs that deter substance and drug abuse.
复制标题
DOI：
10.1517/17460441.2014.956721
复制
发表时间：
2014-11
影响因子：
6.3
通讯作者：
Simeonov A
中科院分区：
文献类型：
--
作者：
Yasgar A;Simeonov A
关于药物滥用及其多方面性质的专题，包括社会的作用及其习俗和法律、经济因素以及负担的程度和性质，已经提出了许多意见并进行了辩论。鉴于涉及成瘾相关认知和行为过程调节的受体和途径的复杂性，近年来已经询问了大量的分子靶点，以发现开发小分子干预措施的起点。本综述介绍了药物滥用干预早期发现领域的最新进展，特别强调了2012-2014年期间发表的进展。从技术上讲，药物滥用药物发现中使用的程序/平台与其他疾病领域使用的程序/平台几乎相同。药物滥用研究中的一个关键复杂因素是围绕所涉及的大脑过程的巨大生物复杂性，以及在寻找“好”靶点和实现治疗剂的精确选择性方面的相关困难。虽然近年来在利用高通量技术的力量发现许多新目标的原理证明分子方面取得了巨大进展，但下一代模型在这一领域将特别重要;例子包括寻求有利的药物-药物组合，使用自动化的全动物行为筛选系统，推进我们对表观遗传学在药物成瘾中的作用的理解，以及类器官水平3D测试平台（也称为组织芯片或芯片上器官）的使用。
Much has been presented and debated on the topic of drug abuse and its multidimensional nature, including the role of society and its customs and laws, economical factors, and the magnitude and nature of the burden. Given the complex nature of the receptors and pathways implicated in regulation of the cognitive and behavioral processes associated with addiction, a large number of molecular targets have been interrogated during recent years to discover starting points for development of small molecule interventions. This review describes recent developments in the field of early drug discovery for drug abuse interventions, with a special emphasis on advances published during the 2012-2014 period. Technologically, the processes/platforms utilized in drug abuse drug discovery are nearly identical to those used in the other disease areas. A key complicating factor in drug abuse research is the enormous biological complexity surrounding the brain processes involved and the associated difficulty in finding “good” targets and achieving exquisite selectivity of treatment agents. While tremendous progress has been made during recent years to use the power of high-throughput technologies to discover proof-of-principle molecules for many new targets, next-generation models will be especially important in this field; examples include seeking advantageous drug-drug combinations, use of automated whole-animal behavioral screening systems, advancing our understanding of the role of epigenetics in drug addiction, and the employment of organoid-level 3D test platforms (also referred to as tissue-chip or organs-on-chip).