Phosphodiesterase inhibitors for the treatment of erectile dysfunction.

The key event in penile erection is relaxation of the cavernous smooth muscle. As phosphodiesterases (PDEs) are key enzymes of the signaling pathway, knowledge about cavernous PDEs is of major importance in understanding the effects and side-effect profile of new and selective pharmacological agents for erectile dysfunction. Experimental studies revealed that gene transcripts of 14 different PDE isoenzymes are present in human cavernous tissue. Of these, PDE3 and 5 have the most prominent functional role. The effects and side effects of clinically available PDE5 inhibitors can be explained both by the distribution pattern of these two isoenzymes in various tissues, by direct inhibition of PDE5 and indirect inhibition of PDE3 in various tissues, and by the putative selectivity for a cavernous-specific PDE splice variant.