Phosphodiesterase type 5 inhibition in erectile dysfunction: an overview

Widely distributed throughout the body, cyclic nucleotide phosphodiesterases (PDEs) are functionally heterogeneous enzymes with potential roles in a number of physiological actions. Among these enzymes, PDE type 5 has received particular attention because of the widespread use of the PDE5 inhibitor sildenafil citrate as an oral therapy for erectile dysfunction. Within the corpus cavernosum of the penis, PDE5 catalyzes the enzymatic degradation (inactivation) of cyclic 3′,5′-guanosine monophosphate, which is a second messenger and key mediator of vascular and trabecular erectile tissue smooth muscle relaxation. By amplifying the nitric oxide-cyclic nucleotide signalling pathway, PDE5 inhibitors serve as ‘contingent agonists’ of the physiological response to sexual arousal. In experimental models, tadalafil increased the sensitivity of penile resistance arteries and erectile tissues to three stimuli of smooth muscle relaxation, namely electrical field stimulation, sodium nitroprusside, and acetylcholine. In randomized, double-blind, placebo-controlled trials, sildenafil and the investigational agents tadalafil and vardenafil significantly enhanced erectile function in the majority of patients and were well tolerated.