Phosphodiesterases in the CNS: targets for drug development

被引：327

作者：

Menniti, Frank S.

Faraci, W. Stephen

Schmidt, Christopher J. ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, CNS Discovery, Groton, CT 06340 USA

[2] Pfizer Global Res & Dev, Res Technol Ctr, Cambridge, MA 02139 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2006年 / 5卷 / 08期

关键词：

D O I：

10.1038/nrd2058

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：660 / 670

页数：11

共 99 条

[31] Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3:: alternative splicing of mRNA transcripts, genomic structure and sequence [J].