Phosphodiesterase type 5 inhibitors as a treatment for erectile dysfunction: Current information and new horizons

Abstract

Introduction: Over the past 15 years, the discovery and development of oral medications that selectively inhibit the enzyme phosphodiesterase type 5 (PDE5) have revolutionised the treatment of erectile dysfunction (ED). Currently, three PDE5 inhibitors are widely available clinically, i.e., sildenafil, vardenafil and tadalafil. New PDE5 inhibitors, including avanafil and udenafil, are now in clinical use in a few countries, and other compounds are under development.

Methods: We describe the current use and future direction of PDE5 inhibitors in the treatment of ED.

Results and conclusion: Each PDE5 inhibitor has an excellent and comparable efficacy and tolerability. These drugs are highly effective for ED of various causes, and are effective in preventing ED after radical prostatectomy. However, whilst being at least 60% effective, PDE5 inhibitors are still ineffective in at least 30% of patients, prompting current research into other pharmacological targets for ED.

Keywords: Cmax, maximum serum concentration; ED, erectile dysfunction; Erectile dysfunction; FDA, USA Food and Drug Administration; GTP, guanosine triphosphate; IIEF, International Index of Erectile Function; NO, nitric oxide; PDE5(i), phosphodiesterase type 5 (inhibitors); Penile disorders; Phosphodiesterase type 5 inhibitors; RCT, randomised controlled trial; SHIM, Sexual Health Inventory in Men; Tmax, time to Cmax; cGMP, cyclic guanosine monophosphate; sGC, soluble guanylyl cyclase.

Figure 1

PDE5i promote penile smooth muscle cell relaxation and erection by preventing the degradation of cGMP.

Figure 2

The multifactorial causes of ED.

Figure 3

The molecular structures of clinically available PDE5i.