Reuillon Tristan, Ward Simon E, Beswick Paul
Sussex Drug Discovery Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QJ, UK.
Curr Top Med Chem. 2016;16(29):3536-3565. doi: 10.2174/1568026616666160627114507.
The neurotransmitter glutamate and its receptors have long been of interest to scientists involved in pharmaceutical research since dysfunction of the glutamatergic signalling pathway has been associated with the pathophysiology of several psychiatric and neurological disorders. The research on AMPAR positive allosteric modulators offers opportunities to modulate fast excitatory synaptic transmission and identify new potential therapeutic agents for a range of neurodiseases. The field of AMPAR modulators continues to be a dynamic area of drug discovery with a pronounced diversification of the chemotypes explored in recent years. This article reviews literature published in this area in the last 6 years, focusing on the new core templates, some derived from high-throughput screens, with an emphasis on structure-activity relationships, drug metabolism and pharmacokinetics properties, and pharmacological profiles of these series.
长期以来，参与药物研究的科学家们一直对神经递质谷氨酸及其受体感兴趣，因为谷氨酸能信号通路功能障碍与多种精神和神经疾病的病理生理学有关。对AMPA受体正向变构调节剂的研究为调节快速兴奋性突触传递和识别一系列神经疾病的新潜在治疗药物提供了机会。AMPA受体调节剂领域仍然是一个充满活力的药物发现领域，近年来所探索的化学类型有显著的多样化。本文综述了过去6年该领域发表的文献，重点关注新的核心模板，其中一些来自高通量筛选，强调这些系列的构效关系、药物代谢和药代动力学性质以及药理学概况。
