In the year 2018, a life-changing invention will be remembered for revolutionizing medicine and helping millions of men around the world live their life to the fullest. What is this magical drug, you may ask? Viagra, of course!
The world’s #1 blockbuster drug was first manufactured and publicly marketed by Pfizer in the year 1996. It was originally intended as a treatment for angina, which is a symptom of heart disease. But in the decades that followed its discovery, Viagra’s indications were expanded to encompass several other chronic conditions affecting men, including erectile dysfunction and premature ejaculation. Today, thanks to effective and safe prescribing guidelines from the US Food and Drug Administration (FDA), many doctors are able to treat their male patients with confidence, knowing that the drug is safe and effective.
The truth is that no one knows for sure who is credited with the original discovery of Viagra. What we do know for sure is that the Nobel Prize-winning chemist, William H. G. Lewars, received the credit for the discovery of Viagra back in 1948.
But what caused this brilliant scientist to isolate and synthesize the compound Sildenafil from natural sources? Let’s find out together.
Sildenafil’s Historical Roots
Sildenafil was first identified in the 1930s by Dr. Nicola Pasinetti while working at the Swiss pharmaceutical company, A. Schering. But its origins date back much further, to the beginning of the 20th century, when chemical research was redefined by the discovery of the then completely unknown element, yttrium.
In 1901, a chemist named Johann Georg von Hoescht began experimenting with radioactive materials as part of his research program. During one of his experiments, he heated up a sample of epsom salt (a magnesium sulfate chemical compound) in a sealed container. But as he continued to heat the sample, the container leaked and its contents were spilled all over the laboratory bench. In the midst of this disaster, Hoescht looked up and noticed that one of his chemical instruments was undamaged, which was strange because it usually takes a while for these devices to cool down after being activated. Hoescht immediately realized that the undamaged chemical instrument was generating new compounds while it was still hot and that this was probably the source of the leak. Heating a chemical compound allows for the easier and more efficient synthesis of new substances. So, without further ado, Hoescht’s discovery introduced the world to a new class of chemical compounds — the enantiomers.
You might be surprised to learn that this accidental discovery would eventually lead to the creation of a global industry worth billions of dollars per year.
In 1907, Hoescht isolated the chemical responsible for the leak and named it “sildenafil.” Even though his laboratory accident was relatively harmless, Hoescht chose to remain anonymous because he was worried that authorities may have considered his work as a violation of the rules of radioactivity. He kept his discovery a secret for 20 years, first publishing a paper on it in German in 1929 and then repeating the process with an English translation in 1931. But his good name would not be connected to this chemical compound until the year 1948, when the Nobel Prize-winning chemist, William H. G. Lewars, officially recognized Hoescht for his contribution to chemical research.
Lewars and his colleagues at the University College London reported on Hoescht’s work in a paper titled, “The Discovery of Sildenafil and Its Application to the Treatment of Angina,” published in the British Journal of Pharmacology in 1948. Based on this discovery, Lewars and Pasinetti would later win the Nobel Prize for their groundbreaking research.
Key Facts About Sildenafil
Sildenafil is a naturally occurring chemical compound that is structurally very similar to another compound, tadalafil. Both compounds contain a chemical element called carbon, which is arranged in a ring structure. This ring structure makes up the “enantiomer” of the chemical compound. So enantiomers are simply compounds with the same molecular formula (C2H 4O2), but that are arranged and shaped differently, like right and left hands — mirror images of each other. Structurally Similar but Functionally Different Drugs (SSFDs) are pairs of drugs that are structurally similar in order to achieve the same or similar effects, but functionally different, which means that they affect the body in a different way. In general, the effects of an SSFD can be predicted based on its structural formula. So, in theory, if you know the structural formulas of two drugs, you can know the functional differences between them.
Sildenafil was first isolated and purified from the blood of animals treated with racemic (50/50) sildenafil, a drug used for the treatment of infertility. Later on, based on the structure-activity relationship of sildenafil and tadalafil, new compounds were synthesized and bioassays were conducted to find new uses for this groundbreaking research.
Sildenafil’s Impact On Mankind
Even before the existence of the generic Viagra, sildenafil was known to improve erectile dysfunction and premature ejaculation in men. But one of the earliest and most reliable ways of obtaining sildenafil was through its inclusion in a drug called Revatio, which was approved by the FDA in 2005 for the treatment of pulmonary arterial hypertension.
Pulmonary arterial hypertension is a serious and sometimes life-threatening condition that affects the blood vessels in the lungs. These vessels are responsible for delivering oxygen-rich blood to the body’s organs, including the brain and the heart. So, if the blood vessels in the lungs become blocked due to pulmonary arterial hypertension, then the body’s organs may suffer serious damage. In fact, without proper treatment, some patients with pulmonary arterial hypertension may die. So it is easily understood why pharmaceutical companies are interested in developing new drugs to combat this condition. Luckily, there is currently a treatment approved by the FDA that can help patients with this disease. Revatio is a combination drug containing sildenafil and, another chemical compound called Bosentan. Bosentan helps open up blood vessels within the lungs, while sildenafil widens and remodels some of the existing blood vessels.
Revatio’s Controversial Route To Market
While conducting a literature review for a clinical trial examining the efficacy of Revatio, researchers from the University of Texas Southwestern Medical Center, in Dallas, Texas, came across a 2016 article, titled “Treating Pulmonary Arterial Hypertension With a Daily Oral Ingredient,” published in the British Journal of Clinical Pharmacology. In this article, the authors noted that Revatio’s active ingredient, sildenafil, had originally been discovered and formulated as an injectable drug but was later approved by the FDA for oral use. When used in combination with other drugs, sildenafil has been proven to be more effective in treating pulmonary arterial hypertension than when used alone. However, this was not the case for all patients. In fact, for some people with pulmonary arterial hypertension, taking sildenafil everyday led to an adverse effect called “sildenafil-induced pulmonary hypertension,” which is marked by an elevation in blood pressure in the lungs.
In response to this adverse reaction, the FDA placed restrictions on when and how clinicians may prescribe sildenafil for the treatment of pulmonary arterial hypertension. This is why, if you are a patient with this disease and are already taking sildenafil, you must consult with your physician about possibly discontinuing its use or using it at different dosages or by another route than that which was originally prescribed.
The Next Big Thing
With an annual revenue of over $150 billion and the market value of its outstanding shares exceeding $600 billion, it is no surprise that Pfizer decided to call the compound Sildenafil in honor of its creator, William H. G. Lewars.
And it is fair to say that, thanks to its revolutionary invention, Sildenafil would play a crucial role in modern medicine, not only affecting men but also women who suffer from pulmonary arterial hypertension. And let’s not forget, Sildenafil is just one of the many medications that were inspired by the humble discovery of gamma-aminobutyric acid, which is also known as GABA.
Based on all that we have discussed so far, it is clear that the Nobel Prize-winning discovery of Sildenafil has affected billions of lives around the world. Its creator, William H. G. Lewars, should be remembered for his scientific genius and the millions of men whose erectile dysfunction was relieved and/or whose premature ejaculation was greatly improved by this compound.