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If you want to create a drug that increases blood flow to the penis, there are at least three ways to do it:
Increase the amount of nitric oxide produced in the penis
Increase the amount of cGMP produced in the penis in response to the nitric oxide
Eliminate the PDE in the penis so that the cGMP builds up instead of getting decomposed by the PDE
The Nobel Prize
In 1998, three scientists — Robert F. Furchgott, Dr. Ferid Murad and Louis J. Ignarro — won the Nobel Prize in Physiology or Medicine for showing that nitric oxide acts as a signaling device between cardiovascular cells. See NobelPrize.org: The Nobel Prize in Physiology or Medicine 1998 to learn more.
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Viagra uses method No. 3 — it eliminates the PDE that is decomposing the cGMP, so cGMP builds up in the penis and has a larger effect on the artery walls. The greater the amount of cGMP the greater the blood flow, and the greater the blood flow the greater the degree of the erection.
The reason that Viagra uses this technique is because of an interesting quirk of PDE.
It turns out that the human body has at least 11 different kinds of PDE that it produces. Only one of those kinds of PDE — PDE5 — is found primarily in the penis. Once scientists discovered this fact, the creation of Viagra®was relatively simple. All that Pfizer needed to find was a chemical that would selectively block PDE5 and nothing else. With the PDE5 blocked, cGMP could build up in the penis and increase the blood flow there without affecting other parts of the body.
If there were not a unique type of PDE found in the penis, we would not have Viagra today.
So how does Viagra block PDE5?
PDE5 is what is known as an enzyme. An enzyme is a specially folded protein that can speed up a chemical reaction. For example, the article How Cells Work describes the maltase enzyme. Maltase is shaped so that a maltose molecule can fit right in, and when it does, the maltase enzyme breaks the maltose molecule into two glucose molecules, as shown here:
PDE5 is an enzyme that accepts cGMP and breaks it down. Pfizer needed a chemical that would gum up PDE5 and keep it from doing its job. The chemical that Pfizer discovered is called sildenafil citrate. It fits right into the PDE5 enzyme and disables it.
Viagra contains sildenafil citrate packaged as a pill. When a man takes a Viagra pill, the sildenafil citrate flows throughout his body, but it really only affects the PDE5 enzyme in the penis. The drug stays in the bloodstream for about four hours, and then it is washed out of the blood by the liver and kidneys.
And that’s the end of the “how it works” part of the Viagra story:
A man takes a Viagra pill.
The sildenafil citrate enters his bloodstream and flows throughout his body.
The sildenafil citrate attaches to the PDE5 enzyme in his penis and disables most of it.
When the man becomes sexually aroused, the brain sends the normal message to the NANC cells in his penis, which produce nitric oxide as usual.
The nitric oxide creates cGMP, which starts relaxing the arteries in his penis.
Since the PDE5 has been disabled, the cGMP in the penis does not break down. Instead, it builds up and lets the arteries in the penis fully dilate.
His penis inflates with blood, and the man gets a full erection.
This works perfectly for the majority of men, except for a few minor problems…
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