Rev Neurosci. 2014;25(3):451-67. doi: 10.1515/revneuro-2014-0030.
5-Hydroxytryptamine (5-HT, serotonin) subtype 6 receptor (5-HT6 receptor, 5-HT6 R) belongs to a 5-HT subclass of a relatively wide G protein-coupled receptor (GPCR) family. Accumulated biological data indicate that 5-HT6 R antagonists and agonists have a great potential for the treatment of neuropathological disorders, such as Parkinson's disease, Alzheimer's disease, and schizophrenia. A number of painstaking efforts have been made toward the design of novel 5-HT6 R ligands; however, there are still no drugs that successfully passed all the clinical trials and entered the market, except for several multimodal ligands. Novel active molecules are strongly needed to progress this development forward. The in silico drug design has some benefits compared with the other rough approaches in terms of thoroughness and predictive accuracy; therefore, it can be effectively used as a solid foundation for the design of novel 5-HT6 R ligands with high potency and selectivity. Here, we provide an overview of the reported computational approaches to the design of novel 5-HT6 R ligands.
5-羟色胺（5-HT，血清素）亚型 6 受体（5-HT6 受体，5-HT6R）属于相对广泛的 G 蛋白偶联受体（GPCR）家族的 5-HT 亚类。积累的生物学数据表明，5-HT6R 拮抗剂和激动剂在治疗神经病理疾病方面具有巨大的潜力，如帕金森病、阿尔茨海默病和精神分裂症。人们为设计新型 5-HT6R 配体付出了许多艰苦的努力；然而，除了几种多模式配体外，仍然没有一种药物成功通过所有临床试验并进入市场。需要新型的活性分子来推动这一发展。与其他粗略方法相比，基于计算机的药物设计在全面性和预测准确性方面具有一些优势；因此，它可以有效地作为设计高活性和选择性新型 5-HT6R 配体的坚实基础。在这里，我们提供了对新型 5-HT6R 配体设计的报道计算方法的概述。
