The future is today: emerging drugs for the treatment of erectile dysfunction

Abstract

Erectile Dysfunction (ED) is the most common male sexual dysfunction presented for treatment, and the most thoroughly studied sexual dysfunction in men. In the late 20th century, important discoveries were made regarding both the physiologic processes of penile erection and the pathophysiology of ED. These discoveries led to the commercial introduction of the phosphodiesterase type 5 inhibitors (PDE5I), a class of medications which now accounts for the largest segment of the ED market. While these drugs are highly efficacious for many men, a relatively large subset of ED patients who do not respond to PDE5I has been identified. Recognition of this subset of the ED population and the ageing of the population has driven researchers to investigate novel treatment targets for ED. Increased research efforts have resulted in the development of several orally available compounds that combine high efficacy with low rates of adverse events. In this review we report on various compounds that regulate penile erection both centrally (Clavulanic acid, Dopamine and Melanocortin receptor agonists) and peripherally (novel PDE5I, soluble and particulate Guanylil Cyclase activators, Rho-kinase inhibitors and Maxi-K channel openers), and discuss the preclinical and clinical evidence supporting the development of these emerging drugs for ED.

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

“…Modulation of ventral striatal activation by the subjectively perceived sexual intensity of a stimulus has been described before (Walter et al, 2008a), and changes in activity of the ventral striatum have been reported in various contexts of a rewarding sexual stimulation (Hamann et al, 2004;Stark et al, 2005). Dopamine agonists have been shown to induce penile erection in animals and humans (Carson, 2007) and have been suggested as promising agents for the treatment of sexual dysfunction (Albersen et al, 2010). Dopamine agonists have further been related to hypersexuality in the treatment of Parkinson's disease (for review, see Voon et al, 2009).…”

Evaluation and Treatment of Erectile Dysfunction in the Aging Male: A Mini-Review

“…For a more elaborate discussion, we refer the reader to references [13] and [14] . Penile erection is a complex neurovascular phenomenon under hormonal control.…”

“…Calmodulin in turn dissociates from myosin light chain kinase, thus inactivating it in turn leading to smooth muscle relaxation, and ultimately, to penile tumescence. Figure and legend adapted from Albersen et al [14] .…”

Association of lower urinary tract symptoms and erectile dysfunction: pathophysiological aspects and implications for clinical management

“…The discovery of the NO signaling pathway in penile tissue has led to a Association of lower urinary tract symptoms and erectile dysfunction H Orabi et al revolution in ED research and to the development of phosphodiesterase-5 (PDE5) inhibitors, which now constitute first-line therapy for men with ED. 13 In recent years, it has been recognized that reduced NO availability is linked to the development of prostate gland hyperplasia and the subsequent development of LUTS. As a logical result, there is an increasing interest in the NO pathway as a potential pharmacological target to treat male LUTS.…”