Phosphodiesterase inhibitors in the treatment of erectile dysfunction

Based on knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation and the development of new and selective pharmacological agents, selective phosphodiesterase (PDE) inhibitors were recently introduced in the treatment of erectile dysfunction. The presence of mRNAs specific for 13 different human phosphodiesterase isoenzymes and isoforms in human cavernous tissue was shown by RT-PCR. We detected an expression of the following genes encoding for both cAMP and cGMP hydrolyzing PDEs: all three isogenes of PDE I and PDE IIa, which do hydrolyze cAMP as well as cGMP; the specific cAMP hydrolyzing PDEs PDE IIIa, the four isogenes of PDE IV, PDE VIIa and PDE VIIIa and the cGMP-specific PDEs PDE Va and PDE IXa. By protein chemical methods, PDE-isoenzymes III, IV and V were characterized in the human cavernous smooth muscles. In functional organ bath studies using precontracted human cavernous tissue strips, PDE III and V inhibitors showed the most pronounced relaxant responses. In clinical studies, the use of the orally active PDE V inhibitor sildenafil induced a pronounced and significant erectogenic effect in patients both with predominantly psychogenic and organogenic etiology of erectile dysfunction. The first promising clinical data of the use of an orally active PDE inhibitor for the treatment of erectile dysfunction are well supported by consistent basic scientific findings. Further research will possibly allow to identify diagnostic tools for erectile dysfunction and for even more selective drugs in its therapy.