Neuroscience Research Unit, Pfizer, Inc., Groton, CT 06371, USA.
Curr Top Med Chem. 2010;10(2):222-30. doi: 10.2174/156802610790411009.
As might be predicted for an organ designed for cell to cell communication, cyclic nucleotide signaling in the brain is highly organized and regulated. Augmentation of cyclic nucleotide signaling by means of phosphodiesterase inhibition appears to be a viable and tractable means of enhancing neuronal communication. Of the various CNS disorders that have been considered as target indications for phosphodiesterase inhibitors, no condition has received more attention than cognitive dysfunction. This review provides a background for understanding the expanding literature in this field as well as a brief update on the rationale driving the search for selective inhibitors of targets such as PDE1B, PDE2, PDE5 and PDE9.
由于这个器官是为细胞间通讯而设计的,因此大脑中的环核苷酸信号具有高度的组织性和调节性。通过抑制磷酸二酯酶来增强环核苷酸信号似乎是一种可行且可行的方法,可以增强神经元通讯。在被认为是磷酸二酯酶抑制剂的各种中枢神经系统疾病中,没有一种疾病像认知功能障碍那样受到更多关注。本综述为理解该领域不断扩展的文献提供了背景知识,并简要介绍了推动寻找 PDE1B、PDE2、PDE5 和 PDE9 等靶标选择性抑制剂的基本原理的最新进展。