Cyclic guanosine monophosphate-specific phosphodiesterase (PDE5 (for the main therapeutic cGMP-specific enzyme in humans))

Cyclic guanosine monophosphate-specific phosphodiesterase (most commonly referring to PDE5 in humans) is an enzyme responsible for the hydrolysis of the intracellular second messenger cGMP, thereby regulating its cellular levels and downstream signaling. PDE5 is highly expressed in the corpus cavernosum, vascular smooth muscle, and certain other tissues, including the retina and heart. By controlling the breakdown of cGMP, PDE5 modulates vascular tone, cardiac function, and aspects of neuronal signaling. Inhibition of PDE5 is therapeutically exploited to manage erectile dysfunction, pulmonary arterial hypertension, and other disorders. Selective PDE5 inhibitors, such as sildenafil and tadalafil, increase cGMP levels, promoting smooth muscle relaxation and vasodilation while minimizing off-target effects compared to earlier non-selective inhibitors. Mutations or dysregulation of PDEs, particularly in photoreceptor cells, are also implicated in some retinal diseases. The safety profile is generally favorable but includes risks of hypotension and drug interactions, particularly with nitrates[2][5][6][7][8].

Other names

cGMP-specific phosphodiesterasePhosphodiesterase type 5PDE5cGMP-PDEcGMP 3',5'-cyclic phosphodiesteraseEC 3.1.4.17

Inhibition of PDE5 prevents the breakdown of cGMP, leading to increased cGMP levels. Enhanced smooth muscle relaxation via vasodilation (therapeutic action for erectile dysfunction and pulmonary hypertension). Allosteric regulation by cGMP and conformational switching. Modulation of signal transduction in cardiovascular and neurological tissues.