In 1989 a Pfizer team led by Simon Campbell in Sandwich, Kent synthesized compound UK92480, hoping to treat high blood pressure and angina. Trials at Morriston Hospital in Wales showed almost no effect on chest pain, but researchers led by Ian Osterloh noticed men reporting erections. Pfizer repositioned the drug, patented it in 1996 and won FDA approval in 1998, the same year three scientists won the Nobel Prize for discovering nitric oxide signaling. This episode explains how sildenafil blocks the PDE5 enzyme so cGMP can keep blood vessels relaxed, and why it does nothing without arousal.

The same molecule went on to treat pulmonary arterial hypertension under the name Revatio and is used off label for Raynaud’s phenomenon. The hosts cover its side effects, the lethal drop in blood pressure when combined with nitrates or poppers, and the advertising push with Bob Dole and Pelé that drove sales to nearly 2 billion dollars in 2008. Then comes the shadow market: counterfeit pills, recreational use, athletes, and a 2026 recall of a chocolate syrup secretly laced with sildenafil.

• Blue tinted vision, or cyanopsia, happens because sildenafil also binds PDE6 in the retina
• Patients sometimes stacked several lower dose generic Revatio pills to match an erectile dysfunction dose
• Pfizer’s main US patent expired in 2020 after legal fights with Teva, and the UK began selling Viagra Connect over the counter
• A 2023 Interpol report found illicit erectile dysfunction drugs made up 22 percent of pharmaceutical seizures
• Fakes have contained blue printer ink, amphetamines, boric acid and rat poison