Department of Pharmacology and Department of Cellular and Molecular Neuropharmacology, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Irunlarrea 1, 31080 Pamplona, Spain.
Alzheimers Res Ther. 2013 Apr 22;5(2):15. doi: 10.1186/alzrt169. eCollection 2013.
During the past 20 years, the 5-HT6 receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this receptor have come to light, and it is now quite evident that 5-HT6 receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer's disease.
在过去的 20 年中,5-HT6 受体受到了越来越多的关注,成为改善认知的有前途的靶点。一些具有不同结构的化合物的研究表明,不仅拮抗剂,而且 5-HT6 受体激动剂也可以改善动物模型的学习和记忆。大量描述该受体配体开发的出版物已经问世,现在很明显,5-HT6 受体在相关专利方面具有巨大的药物潜力。然而,5-HT6 受体的功能远比最初定义的复杂。根据现有数据,不同的细胞途径可能会根据所使用的药物而被激活。本文综述了 5-HT6 受体化合物对认知影响的临床前和临床证据。此外,还将描述 5-HT6 受体化合物通过何种生化和神经化学作用来影响认知。总的来说,几种 5-HT6 靶向化合物可以被合理地视为治疗阿尔茨海默病的有效药物候选物。