How was Viagra discovered? Through a side effect. In 1992 Pfizer was testing sildenafil, then a possible angina medicine called UK-92,480, in healthy volunteers, and "Some volunteers also reported penile erections as a side effect". Pfizer tried it in men with erectile dysfunction from late 1993, and Viagra was approved in 1998.
Who discovered Viagra?
A Pfizer team at Sandwich, in Kent, UK. "In 1986 Pfizer formed a project team of scientists at Sandwich, with the aim of developing a selective inhibitor of PDE5", an enzyme that breaks down cGMP, the chemical messenger that relaxes the muscle in blood vessel walls. The team made a compound "initially named UK-92,480, but is now better known as sildenafil"; it was selected for development in 1989 and "eventually entered clinical trials in 1991" (Ghofrani et al., Nature Reviews Drug Discovery, 2006). The aim was a heart medicine: the work was "part of a programme seeking drugs for angina pectoris" (same review). What that original purpose was, and what became of it, is on what was Viagra's original purpose?
What did the first trials show?
Modest effects on blood vessels, and a warning about nitrates. In 1991, healthy volunteers took single doses of up to 200 mg; at moderate and higher doses there were small falls in blood pressure and "side effects associated with vasodilatation (such as headache and flushing)", and at 150 mg and above "transient disturbances in colour vision perception". In patients with angina, a dose given into a vein had "a moderate vasodilatory effect". A study with glyceryl trinitrate (GTN), a nitrate used for angina, found that sildenafil "augmented the vasodilatory and antihypertensive effects of GTN", so it "would have to be contraindicated in patients taking nitrates" (Ghofrani et al.). It still is: people who use nitrates must not take medicines like Viagra (healthdirect).
When was the side effect noticed?
In 1992, in studies of repeated doses. Healthy volunteers took up to 75 mg three times a day for 10 days; some "reported headaches, flushing, indigestion and muscle aches. Some volunteers also reported penile erections as a side effect." Pfizer did not act on it at once: "Initially this was not considered to be of major significance", and "cardiovascular indications remained the primary focus of ongoing clinical investigations during 1992 and 1993". By mid-1993 the angina work was "looking less promising" (Ghofrani et al.). Older accounts, this page's earlier version among them, place the erections in angina patients; the published record places them in healthy volunteers.
Why did the side effect make sense?
Because of new research on how erections work. The review notes that "in the early 1990s, Ignarro and others reported that NO is the neurotransmitter that is released from cavernous nerves during sexual stimulation". Nitric oxide, the NO in that sentence, raises cGMP in the penis, and PDE5 breaks cGMP down, so "The Pfizer team postulated that the administration of an inhibitor of cGMP breakdown would enhance and prolong the vasodilatory response, but only during sexual stimulation" (Ghofrani et al.). That is still how Viagra works: sexual stimulation is required for it to work (EMA — Viagra). At the time, a tablet that worked seemed unlikely: "few researchers and clinicians in the field thought this was possible" (Ghofrani et al.).
How was it tested in men with erectile dysfunction?
In small studies first, then a large programme. "In late 1993 the first clinical study in patients with ED was undertaken", using a device that recorded the hardness of the penis during sexual stimulation, and "By mid-1994, after completion of two separate clinical studies, single doses of sildenafil were shown to enhance erectile responses to sexual stimulation" (Ghofrani et al.). Pfizer's Sandwich researchers published one early study in 1996: in "12 patients with erectile dysfunction without an established organic cause", sildenafil enhanced "the erectile response (duration and rigidity of erection) to visual sexual stimulation" (Boolell et al., International Journal of Impotence Research, 1996). "By 1997 more than 4,500 subjects had been exposed to sildenafil, and 21 separate clinical trials had demonstrated the efficacy of sildenafil in various patient populations"; the FDA approved Viagra in March 1998, and "European approval followed in September 1998" (Ghofrani et al.). The exact dates, and when it reached Australia, are on when was Viagra introduced to the market?
Where does this story come from?
Mostly from Pfizer's own people. The fullest published account, the 2006 review quoted on this page, was co-written by Ian Osterloh; its competing-interests statement says he "was responsible for the clinical development of Viagra for erectile dysfunction" and was a full-time Pfizer employee when it was published (Ghofrani et al.). The 1996 study came from "Pfizer Central Research, Sandwich, Kent, UK" (Boolell et al.). It is a detailed record, and it is the company's own.
The short answer
Viagra was discovered by accident. Pfizer scientists in Sandwich, UK, developed sildenafil from 1986 as a possible angina medicine; in 1992 healthy volunteers reported erections as a side effect, the angina work faded by 1993, and trials in men with erectile dysfunction from late 1993 led to Viagra's approval in 1998. The rest of the story is in our history of Viagra, and how generic versions arrived is on is generic Viagra available in the USA?
