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.
Küthe
Andrea
A
Department of Urology, Medizinische Hochschule, Hannover, Germany.
Montorsi
Francesco
F
Andersson
Karl-Erik
KE
Stief
Christian G
CG
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000032:analysis; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010413:Penis / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000502:physiology
D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human