text: PDE5 is an enzyme that was first purified in 1980 from a rats lung. PDE5 converts intracellular cGMP to the nucleotide GMP. Many tissues contain PDE5, such as lungs, kidneys, brain, platelets, liver, prostate, urethra, bladder and smooth muscles. Because of the localization of PDE5 in the smooth muscle tissue, inhibitors were developed for the treatment of erectile dysfunction along with pulmonary hypertension.
  Sildenafil was initially introduced for clinical trial in 1989. It was the result of extensive research on chemical agents targeting PDE5 that could be effective in treatment of coronary heart disease.  Sildenafil did not prove effective for coronary heart disease but an interesting side effect was discovered, a penile erection. That side effect soon became the main field of investigation.  The inhibitor is highly selective for the PDE5 family.
  Sildenafil is a prototype of PDE5 inhibitors that Pfizer launched as Viagra. It was approved by the Food and Drug Administration (FDA) in 1998 as the first oral medicine for erectile dysfunction. Later, in the year 2005, it was approved for the treatment of pulmonary arterial hypertension. Vardenafil and tadalafil were discovered in 1990. These drugs came out of research programs focusing on finding PDE5 inhibitors for the treatment of cardiovascular diseases and erectile dysfunction. The two PDE5 inhibitors soon became treatments for these conditions.
  Tadalafil is the most versatile inhibitor and has the longest half-life, 17.5 hours. This allows for a longer therapeutic window and is therefore often a more convenient drug than others with a shorter therapeutic window. Tadalafil is more bioavailable (80%) than sildenafil (40%) and vardenafil (15%) but it has a slow absorption, or about 2 hours compared to 50 minutes of sildenfil. Vardenafil is most known for its potency.
  Because of severe adverse effects and patients dissatisfaction with current therapy choices other inhibitors have recently been approved for clinical use. These inhibitors are udenfil, avanafil lodenafil and mirodenafil.