Introduction
As we all known, Phosphodiesterase 5 inhibitors (PDE5i) are widely used in clinical practice. Previous a series of clinical trials published inThe New England Journal of Medicine showed that oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction (ED),1 and no adverse cardiovascular effects in men with severe coronary artery disease.2Moreover, it may improve exercise capacity and hemodynamics in patients with symptomatic pulmonary arterial hypertension (PAH).3 In fact, the use of PDE5i could provide definite cardiovascular benefits beyond ED treatment, including cardioprotective effects and improving acute myocardial infarction (AMI) survival.4 It is now a promising drug candidate for the treatment of not only cardiovascular disease (CVD),5 but also neurocognitive or neurodegenerative disorders due to the potential of neuro-restorative and neuroprotective effects.6,7
Table 1 Major clinical applications and related molecular mechanisms 16-19