Sildenafil Sildenafil (marketed as Viagra) was the first PDE5 inhibitor on the market. Originally created as a treatment for high blood pressure in 1989, it was found to have a secondary use as an effective PDE5 inhibitor, enabling men who use it to gain stronger erections after arousal. The FDA approved Viagra on March 27, 1998. Discovered by Pfizer, sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum in the penis. This means that, when sildenafil is present in the organism, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum, which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, sildenafil should not cause an erection. Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina that is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels. Vardenafil Vardenafil (marketed as Levitra, Staxyn and Vivanza) was the second oral PDE-5 inhibitor for erectile dysfunction to be FDA approved in August 2003. Tadalafil Tadalafil (marketed as Cialis) is a PDE5 inhibitor commonly that, in addition to its use in erectile dysfunction is also used to treat pulmonary arterial hypertension. It has a longer half life than sildenafil of 17.5 hours, allowing it to be taken once a day. Tadalafil "daily" (5 mg) is also used for treatment of benign prostate hyperplasia. In patients with pulmonary arterial hypertension, tadalafil improves symptoms and also slows down the progressive deterioration in breathlessness seen in this condition. Studies have shown that tadalafil is more selective for PDE5 over PDE6 than sildenafil or vardenafil. See also PDE5 drug design PDE5 inhibitor Phosphodiesterase Icariin References External links The cGMP Specific Phosphodiesterase Type 5 Enzyme Pfizer Pharmaceutical New Scientist article on Viagra and the female 'G spot' EC 3.1.4 Enzymes of known structure