Ladies and gentlemen, let me tell you about the cell biology lecture that changed my life. Okay, so maybe it didn’t change my life. But considering that this lesson happened about 4 years ago and I still remember most of the lecture about how Viagra works, that should count for something.

Cell Signaling 101

Now, before I could understand the nitty gritty of how Viagra works to bring men, umm, a little bit of happiness to their nethers, my professor had to teach us about this thing called cell signaling. Basically, the idea is that there is a whole lot of communicating in your body, both between your cells and within them. Signal molecules are released either to the cells’ surfaces or inside of the cells, and the cells do what the signal molecules tell them to do. Should the cells produce a particular protein? There are signal molecules for that. Should the cells produce a particular protein in high amounts? There are signal molecules for that too. Should particular cellular processes speed up or halt altogether? You guessed it. There are signal molecules for that as well.

With trillions of cells in our bodies receiving signals (and even sending signals themselves to other cells), we are hard workers at the microscopic level, our cells receiving endless biochemical input and producing what the signal molecules tell the cells to produce. However, the signaling pathway is often more complex than a simple “signal A leads to product B” scenario with no steps in between. Think of the process like those fun-looking domins patterns that are set up in inventive contraptions. The first domino is knocked down and it triggers a series of reactions with other objects tied into the mix. You can think of cell signaling pathways like that. Just at the cellular level.

So now that we’ve covered Cell Signaling 101, we can now talk about Pfizer, the mastermind behind how Viagra works.

The Cell Signal Pathway in which Viagra Comes into Play

In 1986, the research was underway. Now, believe it or not, Pfizer didn’t originally set out to create an erectile dysfunction treatment. Instead, their task was to look at angina pectoralis (aka chest pain) and study the cell signaling pathway associated with it. This chest pain was the result of the heart not getting enough blood due to the blood vessels’ decreased blood flow (also known as vasoconstriction). In order to get better insight of the problem, researchers looked at a particular signal pathway (see image to the top right) that involves an amino acid–a protein building block–called L-arginine. Thanks to NOS, it helps L-arginine convert to nitrous oxide (also known as N.O.). N.O. then travels from the endothelial cell to the smooth muscle cell, and binds to GC (aka guanylyl cyclase). This binding of N.O. to GC triggers the conversion of GTP to cGMP, the key player in this cascade. When cGMP is not converted into anything else, the smooth muscles relax and the blood vessels open up, allowing for easier blood flow. But when the pesky protein PDE5 binds to cGMP, it converts to GMP. And this is a bad thing. Because of this cGMP-to-GMP conversion, it leads to constricted blood vessels, impeded blood flow, and chest pain.

Since PDE5 is the culprit, the goal is to stop it from binding to cGMP so that cGMP does not convert to GMP, allowing the muscles to relax so the blood vessels can open up, allowing for greater ease of blood flow.

Enter Sildenafil, the drug found inside Viagra that should get this job done. If you remember earlier, I mentioned that certain drugs can prevent processes from happening altogether. Sildenafil, the active ingredient found in Viagra, does that very thing. It acts as an inhibitor, blocking PDE5 from binding to cGMP. In this biochemical game of musical chairs, Sildenafil is the winner, beating out PDE5 to the cGMP chair.

With this cell response game plan on lock, it was time to develop a drug containing Sildenafil and test it out in clinical trials. The results of the trial were a lot like how it feels to go to a vending machine to buy one snack yet you notice another snack being released behind it from the rotating coil. Two snacks for the price of one. In this case, however, the first bag is mostly air than snack, not really worth the purchase. But that second bag? It’s filled all the way up. In a likewise manner, while the drug was not as effective as expected, the opening of blood vessels and increased blood flow still did happen. Just not in the chest region.

It happened just a bit lower in these men…

And just like that, the one eyed monsters awoke from their slumber unexpectedly. And the usefulness of Viagra as we know it was born.

A Little on Erectile Dysfunction

About 30 million men in the United States experience erectile dysfunction (E.D.). It usually occurs in men 60 above. That said, as noted in this article on Psychology Today concerning research in older men and E.D., “While E.D. becomes increasingly common in older men, more than half never develop it. Most older men suffer not [from] E.D. but [from] erection dissatisfaction.”

While E.D. is discussed primarily as an issue that a number of older men have, it is still possible to have E.D. in your 20’s or 30’s, especially if you are obese, suffer from kidney disease, have high blood pressure, or any other cardiovascular condition or disease that affects the ease of blood flow. Youth is not bulletproof when it comes to E.D. In fact, a study exploring E.D. in younger men showed 23 male patients who suffered from it. Their age range? 18-49.

The issue in these young men was not blood supply; there was sufficient blood showing up to get the job done. The issue was that they suffered from venous leakage. When an erection occurs, it’s important that the valves in the penile veins close, disallowing the movement of blood away from the erection so that it is sustained. As the name implies, venous leakage occurs when the venous valves do not close properly and blood is moving in and out of the penile veins instead of staying put. Since this is a different phenomenon than Viagra, this issue is usually treated with an anti-leakage drug, vacuum constriction devices, or surgery.

Outside of venous leakage, millions of men have been able to treat their E.D. thanks to Viagra. Thanks to the knowledgeable experts behind the creation of the drug, they were able to apply their knowledge of biochemical pathways in our bodies, noted the notorious PDE5, and managed to hack it to a man’s advantage (albeit for a reason other than what they may have initially expected). Not all heroes wear capes. Sometimes they are an unexpected champion found inside Viagra. And sometimes, they also bring a little bit of happiness to your nethers. 😉

What are your thoughts on how Viagra works? Share them with me in the comments below.