University of Liege, Drug Research Center (CIRM), Department of Medicinal Chemistry, Liège, Belgium.
Expert Opin Ther Pat. 2013 May;23(5):615-28. doi: 10.1517/13543776.2013.770840. Epub 2013 Feb 13.
AMPA receptors represent an interesting target to develop innovative therapeutic drugs such as positive allosteric modulators, a subclass of modulators known to potentiate the effect of glutamate through this kind of glutamatergic ionotropic receptors. The enhancement of AMPA signals is expected to be beneficial in the management of several neurological disorders, such as depression, schizophrenia, Parkinson's disease and learning-memory deficits linked to Alzheimer's disease. AMPA receptor positive allosteric modulators continue to be the object of intensive research as evidenced by the diversification in the range of chemotypes explored.
This article examines recent discoveries of new AMPA receptor modulators mainly described in the patent literature from 2008 to 2012.
An important challenge is to discover an ideal drug candidate exhibiting appropriate in vivo activity after oral administration with an acceptable safety profile. The future remains promising because such compounds have proved to be able to stimulate the expression of the neurotrophic factor BDNF, a unique property opening interesting perspectives in new therapeutic applications.
AMPA 受体是开发创新治疗药物的一个有趣靶点，例如正变构调节剂，这是一类已知通过这种谷氨酸离子型受体增强谷氨酸作用的调节剂。增强 AMPA 信号有望有益于管理多种神经疾病，如抑郁症、精神分裂症、帕金森病和与阿尔茨海默病相关的学习记忆缺陷。正变构调节剂 AMPA 受体继续成为密集研究的对象，这从 2008 年至 2012 年专利文献中探索的化学型范围多样化就可以看出。
本文考察了最近发现的新型 AMPA 受体调节剂，主要是在 2008 年至 2012 年专利文献中描述的。
一个重要的挑战是发现一种理想的候选药物，在口服后具有适当的体内活性和可接受的安全性。未来仍然充满希望，因为这些化合物已被证明能够刺激神经营养因子 BDNF 的表达，这一独特特性为新的治疗应用开辟了有趣的前景。
