The basics of phosphodiesterase type 5 (PDE5) inhibition in urology

Phosphodiesterase (PDE) isoenzymes hold a central role in controlling levels of the cyclic nucleotide monophosphates cyclic AMP and cyclic GMP, which are important second messengers in many transmitter pathways involved in regulating biological processes in urogenital tissues. The development of the PDE5 inhibitors Sildenafil (Viagra), Vardenafil (Levitra), and Tadalafil (Cialis), combining a high response rate and the advantage of on-demand intake, is the result of the scientific characterization of the physiology of penile erectile smooth muscle. The introduction of these compounds as safe and well-tolerated orally active drugs for the treatment of erectile dysfunction has not only become a worldwide clinical success, but it provided the basis for the development and introduction of several new therapeutic modalities into the management of male and female sexual dysfunction. It has also brought further attention to cyclic nucleotide phosphodiesterases as putative pharmacological targets in a variety of disorders, such as pulmonary arterial hypertension, Raynaud's disease, Peyronie's disease, the so-called benign prostatic syndrome, endothelial dysfunction, disturbances of male ejaculatory function (premature ejaculation), and female sexual dysfunction. Because the concept of taking a pill to cure an illness or relieve disease symptoms has become widely accepted by consumers, pharmacological research and development is focusing primarily on selective orally available drugs that influence peripheral intracellular or central regulatory mechanisms. This review briefly describes the current and evolving advances in the field of PDE5 pharmacotherapy in urology and other fields of medicine.