Perspectives in Pharmacology The Biochemical and Neurologic Basis for the Treatment of Male Erectile Dysfunction

Male erectile dysfunction (MED) is defined as the “inability to achieve or maintain an (penile) erection adequate for sexual satisfaction” (National Institutes of Health Consensus Statement, 1993). Erectile dysfunction occurs in varying degrees in an estimated 20 to 30 million U.S. men and is associated with adverse effects on quality of life, particularly personal well being, family, and social interrelationships (Laumann et al., 1999; Johannes et al., 2000). The worldwide prevalence of MED has been estimated at over 152 million men, and the projections for 2025 suggest a prevalence of approximately 322 million with MED. Recent reports of quality of life data suggest that the importance of MED in contributing to other chronic health conditions such as depression has been largely underestimated (Laumann et al., 1999). The treatment of MED has been revolutionized over the last decade from only surgical options (penile prostheses or revascularization) to intracavernosal and intraurethral administered agents [e.g., prostaglandin E1 (PGE1), papaverine, phentolamine] that paved the way to an effective oral therapy such as sildenafil. The clinical efficacy of oral agents such as sildenafil, apomorphine, phentolamine, IC351, and vardenafil represent the beginnings of noninvasive pharmacological treatment for MED. Over the past 25 years, research on MED has focused on the mechanisms of corpus cavernosum smooth muscle relaxation, and this work has provided the basis for our current knowledge of the physiology of erection. On the other hand, the fields of experimental psychology and neuroscience have also unraveled critical information on the brain areas and the neuroanatomical connections regulating sexual behavior. In view of the latest developments in the clinical arena and the potential utility of several novel molecular targets for the pharmacological treatment of MED (Moreland et al., 2000), this review will summarize biochemical and neural mechanisms that affect corpus cavernosum smooth muscle tone and penile erection.