Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male erectile dysfunction

Based on the increasing knowledge of intracellular signal propagation in ca vernous smooth muscle tone regulation, which is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have re cently been introduced in the treatment of erectile dysfunction. The first promising clinical data on the use of the orally active PDES inhibitor Sild enafil in the treatment of erectile dysfunction were accompanied by boostin g research activities on cavernous intracellular signal transduction and ph osphodiesterase characterization with the aid of molecular biology and prot ein chemistry. The presence of mRNA transcripts specific for 14 different h uman phosphodiesterase isoenzymes and isoforms in human cavernous tissue wa s shown by RT-PCR: Three isogenes of PDE1, PDE2A and 10A, which hydrolyse c AMP as well as cGMP, the cAMP-specific PDE3A, four isogenes of PDE4, PDE7A and PDE8A, as well as cGMP-specific PDEs PDE5A and PDE9A. Using anion excha nge chromatography, the activities of PDE isoenzymes 2, 3, 4, and 5 were de tected in cytosolic supernatants of human cavernous smooth muscle. To date, the efficacy and safety of several next generation PDES inhibitors for use in the; treatment of male erectile dysfunction are under evaluation in vit ro and in vivo. Further research will possibly allow identification of diag nostic tools for erectile dysfunction and of even more selective drugs in i ts therapy.