Worldwide Discovery Research, Cephalon Inc., West Chester, PA 19380, USA.
Curr Top Med Chem. 2010;10(2):207-21. doi: 10.2174/156802610790411036.
Cognitive impairment (CI) has been recognized as a core feature of Alzheimer's disease (AD) and schizophrenia. The 5-HT(6) receptor is an attractive target for the development of cognitive enhancers due to its unique localization and pharmacology. 5-HT(6) receptor antagonists have been shown to modulate multiple neurotransmitter systems and therefore enhance cognition in preclinical studies. This premise translated into the clinical efficacy of the 5-HT(6) receptor antagonist SB-742457 in mild-to-moderate AD patients. Advances in the understanding of the structure-activity-relationship, the design of novel 5-HT(6) receptor ligands and their potential application for the treatment of CI are reviewed.
认知障碍（CI）已被认为是阿尔茨海默病（AD）和精神分裂症的核心特征。5-HT（6）受体由于其独特的定位和药理学，成为开发认知增强剂的有吸引力的靶点。5-HT（6）受体拮抗剂已被证明可调节多种神经递质系统，因此在临床前研究中增强认知。这一前提转化为 5-HT（6）受体拮抗剂 SB-742457 在轻度至中度 AD 患者中的临床疗效。本文综述了对结构-活性关系的理解、新型 5-HT（6）受体配体的设计及其在治疗 CI 方面的潜在应用的进展。
