Title:New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is)
Volume: 23
Issue: 12
Author(s): Giovanni Ribaudo, Mario Angelo Pagano, Sergio Bova and Giuseppe Zagotto
Affiliation:
Keywords:
PDE5, sildenafil, anticancer, multi-target, cystic fibrosis, erectile dysfunction.
Abstract: Background: Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil
and the recently approved avanafil represent the first-line choice for both on-demand
and chronic treatment of erectile dysfunction (ED). In addition to this, sildenafil and tadalafil,
have also been approved for the treatment of pulmonary arterial hypertension. Due to
its expression and localization in many tissues, PDE5 and its regulation has been reported to
be involved in several other diseases. Objective: We aim to provide an updated overview of
the emerging therapeutic applications of PDE5-Is besides ED, taking into account the latest ongoing research
reports. Methods: We searched online databases (Pubmed, Reaxys, Scopus) to lay the bases for an accurate,
quality criteria-based literature update. We focused our attention on most recent research reports, in particular
when supported by pre-clinical and clinical data. Results: The regulation of PDE5 may influence pathological
conditions such as, among the others, heart failure, cystic fibrosis, cancer, CNS-related diseases, diabetes and
dysfunctions affecting male urinary/reproductive system. Conclusion: Sildenafil, vardenafil, tadalafil and the
other chemical entities considered PDE5-Is showed overall positive results and significant improvements in
the studied disease, thus some discordant results, in particular when comparing pre-clinical and clinical data,
have to be pointed out, suggesting that further insights are needed especially to assess the exact molecular
pathway underlying.
