Phosphodiesterases (PDEs) are a superfamily of enzymes. This superfamily is further classified into 11 families, PDE1 - PDE11, on the basis of regulatory properties, amino acid sequences, substrate specificities, pharmacological properties and tissue distribution. Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which leads to several biological processes like effect on intracellular calcium level by the Ca pathway.
Phosphodiesterase 5 (PDE5) is widely expressed in several tissues in the body for example brain, lung, kidney, urinary bladder, smooth muscle and platelets. It is possible to prevent cGMP hydrolysis by inhibiting PDE5 and therefore treat diseases associated with low cGMP levels, because of this, PDE5 is an ideal target for the development of inhibitors. The therapeutic effects of PDE5 inhibition have been demonstrated in several cardiovascular conditions, chronic kidney disease and diabetes mellitus.
The major PDE5 inhibitors (a subset of the phosphodiesterase inhibitors) are sildenafil, tadalafil, vardenafil, and avanafil, and although all share the same mechanism of action each has unique pharmacokinetic and pharmacodynamic properties which dictate their suitability in various conditions and their side effect profile.