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 address 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).

The worldwide market value of ED was $3.2 billion in 2006, with the US market being responsible for two-thirds of global sales. Given the ageing of the general population and direct-to-consumer advertising projecting the desire of men of all ages to maintain an active sexual lifestyle, a market growth rate of 4.9% is expected for the period 2006-2012. Due to increasing demand and prospective market growth, pharmaceutical companies are competing to develop more potent and better tolerated drugs.

In this article we reviewed the current ED market and important or promising targets for pharmacological therapy for ED. A wide variety of molecular targets have been identified and special attention has been given to compounds that bypass the need for endogenous NO production, one of the principle limitations of currently available oral ED medications.

By influencing targets in different pathways leading to the development of penile erection, the various compounds that are currently in development will undoubtedly cause a major change in treatment strategies of ED.

Currently available ED guidelines recommend treatment algorithms that are virtually identical for every patient, regardless of the underlying pathology causing the ED. We expect future strategies to allow treatment protocols tailored to the specific needs of each individual patient, taking into consideration the efficacy of erectile performance enhancement and the potential for adverse events.

This tailored approach may include combination of various emerging drugs to enhance efficacy in difficult-to-treat patients. Individual tailoring of treatment to the specific needs of the patient does require an extensive knowledge of the etiology of ED.

Careful characterization and study of these novel compounds by the physician and pharmacologist treating the increasing population of patients suffering from ED will be essential. We hope this review helps not only the sexual medicine specialist or urologist, but also the general practitioner and pharmacologist in the understanding of emerging drugs for ED.



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