Researchers seek new uses for sildenafil.

Abstract

CHICAGO—Now that time and experience have established the role of sildenafil nitrate (Viagra) in the treatment of erectile dysfunction (ED), researchers are turning their attention to studying how the drug may improve outcomes for other problems, as well as its safety and efficacy when combined with other therapies. Studies presented here at the Annual Scientific Meeting of the American Urological Association in late April found researchers pondering the use of sildenafil in patients with rapid ejaculation, in men with ED and lower urinary tract symptoms, and those undergoing radical prostatectomies. “With the efficacy and safety issues of sildenafil for erectile dysfunction basically settled, from a scientific point of view, you need to explore new frontiers,” said Harin Padma-Nathan, MD, clinical professor at the Keck School of Medicine of the University of Southern California in Los Angeles. Those new frontiers center around sildenafil’s enhancement of nitric oxide, a signaling molecule that controls a diverse range of physiological processes in many tissues. Scientists believe that nitric oxide regulates vascular tone and promotes blood vessel relaxation, and plays roles in the immune system, nervous system, and in inflammation. When stimulated, nitric oxide activates the enzyme guanylate cyclase. This, in turn, increases levels of cyclic guanosine monophosphate (cGMP), which causes smooth muscle relaxation. In the penis, this allows an inflow of blood leading to erection. Another enzyme, phosphodiesterase type 5 (PDE5) degrades the effectiveness of cGMP and its ability to create smooth muscle relaxation (leading to ED). Sildenafil inhibits PDE5, allowing cGMP to function more effectively.