Phosphodiesterase inhibitors as potential cognition enhancing agents

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.