Role of phosphodiesterases in neurological and psychiatric disease.

Cyclic nucleotides such as cAMP and cGMP play a central role in neuronal cell function and are regulated by changes in synthesis and/or degradation. Degradation is regulated by phosphodiesterases (PDEs), a group of enzymes consisting of at least 11 families, several of which have multiple isoforms. As inhibition of PDEs can have profound effects on cell function, there is considerable interest in selective antagonists of these enzymes. Recent work has also revealed that PDEs are heterogeneously distributed, thus making them interesting targets for drug development. In particular, PDE10A may play a role in disorders that involve striatal neurons, such as Huntington's disease and psychosis.