Erectile dysfunction is a condition in which a male cannot obtain or maintain an erect penis. It can result from several medical conditions, including diabetes, radical prostatectomy, vascular insufficiency, nerve damage, or insufficient cyclic guanine monophosphate (cGMP) levels.
Phosphodiesterase type 5 inhibitors
Sildenafil (Viagra®), vardenafil (Levitra®) and tadalafil (Cialis®), may treat ED and as well as pulmonary hypertensive, are selective phosphodiesterase type 5 (PDE-5) inhibitors that bind selectively to PDE-5 and inhibit the binding and subsequent degradation of cyclic GMP (cGMP). Normally, erection results from increased cGMP levels produced by guanylate cyclase, which in turn is upregulated by nitric oxide release after stimulation. By decreasing the degradation of cGMP by PDE-5 enzymes increases the levels of cGMP in the corpus cavernosum and its supply vessels, relaxes the smooth muscle, and enables an erection. Viagra (sildenafil) was the first blockbuster drug for ED treatment in this class, although vardenafil is more potent in vitro. Both sildenafil and vardenafil have structural similarity to cGMP (and the unselective PDE inhibitor caffeine), with which they compete for binding of PDE-5 enzymes. Tadalafil is significantly different in structure but is thought to act by the same mechanism.
83% of men who used sildenafil had at least one episode of intercourse as compared to 45% who received placebo according to a systematic review of randomized controlled trials of using sildenafil. Few randomized controlled trials have compared the different phosphodiesterase inhibitors.
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