Cyclic nucleotide phosphodiesterases (PDEs) hydrolyze the second messengers adenosine and guanosine 3, 5-cyclic monophosphates (cAMP and cGMP) to 5-AMP and 5-GMP.Twenty one of human PDE genes are categorized into 11 families and encode >100 isoforms of PDE proteins via alternative mRNA splicing.Family selective PDE inhibitors have been widely studied as therapeutics for treatment of human diseases, such as schizophrenia and psychosis, The most successful examples of this drug class is the PDE5 inhibitor sildenafil that has been marketed as Viagra(R) for the treatment of male erectile dysfunction and Revatio(R) for the treatment of pulmonary hypertension.In addition, PDE5 inhibitors have been studied for the treatment of various human diseases, including (1) lower urinary tract symptoms (LUTs), (2) benign prostatic hyperplasia, (3) cardiovascular disorders, (4) ischemia-reperfusion, (5) acute adrenergic contractile stimulation, (6) chronic hypertrophy, (7) dysfunction attributable to pressure-overload, and (8) chronic heart failure.Recently, PDE5 inhibitor Viagra has been shown to improve the spatial memory and to decrease Abeta levels in the APP/PS1 mice, suggesting its potential for the treatment of Alzheimers disease.