Tadalafil is a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction, similar to sildenafil; however, tadalafil has a longer duration of action. Sexual stimulation causes the release of nitric oxide (NO) from nerves and endothelial cells into the penis. NO activates the enzyme guanylate cyclase.2 The activation of this enzyme is followed by the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP), activating a cascade of protein kinase-dependent phosphorylation events in smooth muscles, ultimately resulting in the dephosphorylation of myosin light chains within smooth muscle. This activity causes the relaxation of smooth muscle within blood vessels, resulting in the desired vasodilatory effect. Phosphodiesterase-5 breaks down cGMP to GMP. Tadalafil inhibits phosphodiesterase-5, preventing the breakdown of cGMP. This increases the concentration of cGMP, increasing the vasodilation and improving blood flow leading to penile erection. Tadalafil is usually administered orally. It is currently also in use as a therapeutic agent in cardiovascular conditions (e.g. pulmonary arterial hypertension) and being investigated for use in some cancers (as an antihyperplasic agent).

Tadalafil Pathway (New) References