Phosphodiesterase 5 (PDE5) was discovered in the lungs of rats in 1980. It can convert cyclic guanosine monophosphate (cGMP) into guanosine monophosphate (GMP). Elevated cGMP blocks the entry of calcium ions into cells. The decrease in calcium ions causes blood vessels to dilate, thereby lowering overall blood pressure.
In 1985, Simon Campbell and others at Pfizer's Sandwich Branch in the UK planned to lower blood pressure by developing drugs that could increase atrial natriuretic peptide (ANP), a blood pressure-lowering factor.
In 1989, Andrew Bell and others started with an existing low-activity PDE inhibitor, zaplast, and synthesized a small molecule substance UK-92,480, which was 100 times more active than the initial compound. times, believed it could inhibit PDE5 and applied for a patent.
However, Ian Osterloh and others in charge of clinical research observed that some volunteers had "side effects" of penile erection after taking the drug.
After learning of these studies, Pfizer's research team linked NO to the side effects of UK-92480.
After research, it was found that inhibiting PDE5 will convert cGMP into GMP. GMP levels increase until blood vessels dilate and blood volume increases, which can treat ED.
More than 300 people participated in the clinical trial*** and it was a great success. Market research also reported positive results, so Peter Dunn and others developed a new synthesis method through research. In 1996, this product applied for a synthesis patent and a new indication patent, and was named Sildenafil ( sildenafil).
Pulmonary hypertension (which can lead to right heart failure) can also be treated with PDE5 inhibitors. The FDA approved sildenafil for the treatment of pulmonary arterial hypertension in 2005. But the product name is Revatio.
In 2008, sales of sildenafil reached US$1.9 billion. In 2013, Pfizer announced it would sell the drug directly to patients online.