Chemical Sciences, Wyeth Research, Princeton, NJ 08543, USA.
Curr Top Med Chem. 2010;10(2):144-52. doi: 10.2174/156802610790410983.
Nicotinic acetylcholine receptors (nAChR) have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular alpha7 and alpha4beta2 subtype-selective nAChR agonists and partial agonists have been developed as potential candidates for the treatment of schizophrenia, cognitive disorders (including Alzheimer's disease), and inflammation. Further development of positive allosteric modulators and antagonists were also recently reported in the literature. In this review we will cover recent developments focused on the above mentioned nAChR subtypes, starting from the most advanced clinical candidate followed by an overview of literature compounds where potency, selectivity, central nervous system access, pharmacological activity and pharmacokinetic properties are disclosed.
烟碱型乙酰胆碱受体(nAChR)已被强烈认为是治疗精神分裂症和阿尔茨海默病(AD)等疾病认知障碍的治疗靶点。特别是α7 和α4β2 亚型选择性 nAChR 激动剂和部分激动剂已被开发为治疗精神分裂症、认知障碍(包括阿尔茨海默病)和炎症的潜在候选药物。最近的文献还报道了正变构调节剂和拮抗剂的进一步开发。在这篇综述中,我们将介绍最近的研究进展,重点介绍上述 nAChR 亚型,从最先进的临床候选药物开始,然后概述文献中的化合物,披露其效力、选择性、中枢神经系统进入、药理活性和药代动力学特性。