PDE5 inhibitor

Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension.

[1] Phosphodiesterase-5 (PDE5) inhibitors such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) are clinically indicated for the treatment of erectile dysfunction.

[1] PDE5 inhibitors have been used as a second line therapy in severe cases of Raynaud phenomenon when it is related to systemic sclerosis per The European Society for Vascular Medicine guidelines.

[1] Finally, there are concerns that PDE5 inhibitors may increase the risk of neonatal mortality in pregnant women, and trials investigating use of the drugs for fetal growth restriction have been suspended.

[1] The PDE5 inhibitor story begins with the work of the British physician and physiologist Henry Hyde Salter who, in 1886, noticed that his asthma symptoms eased after drinking a strong cup of coffee.

[10] In 1986, Pfizer scientists at Sandwich, UK, started preclinical work on the development of a PDE5 inhibitor (later known as sildenafil citrate) for the treatment of angina.

Sildenafil, tadalafil, vardenafil and avanafil are the main agents marketed globally, although mirodenafil, udenafil, gisadenafil, yonkenafil (tunodafil) and lodenafil are available in some countries.

[1] There are some PDE5 inhibitors, generally not approved by any health regulatory agency, that have been found as undeclared ingredients or adulterants in a variety of supplements which are sold as "natural" or "herbal" sexual enhancement products.

For example, in the penis, NO release at high levels from endothelial cells and penile nerves during sexual stimulation leads to relaxation of the smooth vasculature of the corpus cavernosum, causing vasocongestion and a sustained erection.