Menniti Frank S, Faraci W Stephen, Schmidt Christopher J
Pfizer Global Research and Development, CNS Discovery, Groton, Connecticut 06340, USA.
Nat Rev Drug Discov. 2006 Aug;5(8):660-70. doi: 10.1038/nrd2058.
The therapeutic and commercial success of phosphodiesterase 5 inhibitors such as Viagra, Levitra and Cialis has sparked renewed interest in the phosphodiesterases as drug discovery targets. Virtually all the phosphodiesterases are expressed in the CNS, making this gene family a particularly attractive source of new targets for the treatment of psychiatric and neurodegenerative disorders. Significantly, all neurons express multiple phosphodiesterases, which differ in cyclic nucleotide specificity, affinity, regulatory control and subcellular compartmentalization. Therefore, phosphodiesterase inhibition represents a mechanism through which it could be possible to precisely modulate neuronal activity. In this article, we review the current state of the art in the burgeoning field of phosphodiesterase pharmacology in the CNS.
像万艾可、艾力达和希爱力这样的磷酸二酯酶5抑制剂在治疗和商业上的成功，引发了人们对磷酸二酯酶作为药物研发靶点的新兴趣。几乎所有的磷酸二酯酶都在中枢神经系统中表达，这使得这个基因家族成为治疗精神疾病和神经退行性疾病新靶点的一个特别有吸引力的来源。值得注意的是，所有神经元都表达多种磷酸二酯酶，它们在环核苷酸特异性、亲和力、调节控制和亚细胞区室化方面存在差异。因此，磷酸二酯酶抑制代表了一种可能精确调节神经元活动的机制。在本文中，我们综述了中枢神经系统中磷酸二酯酶药理学这个新兴领域的当前技术水平。
