April 10, 1998

Basic research done at VUMC made impotence pill possible

Basic research done at VUMC made impotence pill possible

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Jackie Corbin, Ph.D., (right) and Sharron Francis, Ph.D., in Corbin's lab. (Photo by Donna Jones Bailey).

Millions of impotent men may benefit from a new drug recently approved by the FDA that restores sexual function without the difficulties of traditional treatments.

The drug, called sildenafil, has been developed and manufactured by Pfizer and boosts the function for those who cannot maintain their erections. Most of the basic science research identifying and cloning the enzyme responsible for sildenafil¹s effect was done at Vanderbilt University Medical Center in the laboratory of Jackie Corbin, Ph.D., professor of Molecular Physiology and Biophysics, Sharron Francis, Ph.D., research professor in Molecular Physiology.

"This is a significant problem not only for the affected men but also for relationships," said Corbin. "This drug will help a lot of men regain their sexual function and alleviate many related problems."

Male erectile dysfunction affects 5 percent of all men and 10 percent of men over 40, and the physiological basis for this dysfunction in most instances is organic rather then psychological, Corbin said.

It has been estimated that only 10 percent of men who are affected by this dysfunction report it to their physicians. Since the announcement of FDA approval for the new drug, it is estimated that 40 percent are now reporting this problem.

"We have definitely already seen an increase in the number of men who are reporting their problems. Once men know that there is a medication that can help them, I think they are much more willing to discuss these problems with their physicians," said Corbin.

In clinical trials, sildenafil has been shown to work in about 70 percent of men who have erectile dysfunction. It is taken orally, which is an improvement over prosthetic devices and injections.

Many patients with erectile dysfunction have high blood pressure as a result of heart disease, diabetes, or other types of vascular disease. It is this high blood pressure that often prevents them from sustaining erections by not allowing the blood vessels in the penis to open completely. When the smooth muscle tissue in cells surrounding the blood vessels of the penis are relaxed, it allows blood to flow in, and cause an erection.

"This was really a drug that we investigated for the treatment of high blood pressure. When it was tested in men, some reported that they were having more and longer erections than usual," said Corbin.

Sildenafil works by inhibiting an enzyme called PDE5, which is responsible for preventing or stopping an erection by destroying the protein cyclic GMP. Sildenafil has its unique effect by preventing the degradation of cyclic GMP by the PDE5 enzyme.

Although cyclic GMP and PDE5 are present in all blood vessels, sildenafil only works on the cells in the penis, which has many scientists wondering why, said Corbin.

It is important to note that sildenafil improves erections, but only in men who already have erectile dysfunction. It also does not alter libido, Corbin said.