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Typical Vasodilator


Researchers in Ian Osterloh's lab at Pfizer stopped work on developing sildenafil citrate as a therapy for chest pain in men in 1992 following unpromising results in a Phase I angina study. They noticed, however, that some of the men taking 50- and 75-mg doses in the trial reported an increased tendency to get erections, suggesting a surprise "act two" for sildenafil. "Gradually, a consensus grew that research should shift from angina to the drug's erectile angle, and the rest is, as they say, history," says Daniel J. Watts, a spokesman for Pfizer.

Viagra was approved by the Food & Drug Administration in 1998 as a therapy for erectile dysfunction (ED), a term for impotence that surfaced in the 1990s. The drug rose swiftly to blockbuster status, achieving sales of $1 billion in its first full year on the market.

Physically, Viagra works by inhibiting an enzyme called phosphodiesterase type 5 (PDE5), which normally cleaves cyclic guanosine monophosphate (cGMP), a compound that promotes smooth-muscle relaxation in the corpus cavernosum, thus enhancing blood flow. This enhances the effect of nitric oxide, a chemical released in response to sexual stimulation. Nitric oxide activates guanylate cyclase, an enzyme that boosts levels of cGMP. Cialis, marketed jointly by Eli Lilly & Co. and Icos, and Bayer Pharmaceutical's Levitra are also PDE5 inhibitors.

The likelihood that PDE5 inhibitors could be applied to the treatment of ED had been noted by Peter Ellis and Nick Terrett, researchers in Pfizer's Discovery Biology Laboratory, Sandwich, England. Both are named in the patent for Viagra.

WORKING BLUE Nascar's Mark Martin is a celebrity front man for Viagra.

WORKING BLUE Nascar's Mark Martin is a celebrity front man for Viagra.

The drug's psychological mechanism is far more nebulous and is still being studied. Abraham Morgentaler, in his book "The Viagra Myth: The Surprising Impact on Love and Relationships," focuses on the drug's effect on relationships. "In particular, it forces couples to decide what is real in their relationships and what is not," he writes. "I have come to see Viagra as providing a window into the psyche of men, and perhaps indirectly into the psyche of women, since women are not immune from unduly high expectations regarding the benefits of Viagra and its potential to provide sexual healing."

As it turns out, drugmakers' expectations from Viagra may also be unduly high. Sales figures last year provide some indication that the drug-induced sexual revolution is sputtering. Sales for all impotence drugs reached $2.7 billion in 2004, at least $1 billion lower than industry analysts forecast two years ago. Viagra's sales slipped 11% last year from the 2003 sales figures. This can partly be blamed on competition from Cialis and Levitra.

There are other pressures, such as the fact that most health insurers do not cover prescriptions for ED medication. It won't help that federal officials recently began looking into reports that Viagra and other impotence drugs are linked to 43 cases of blindness. And some analysts claim that many men are too embarrassed to seek treatment.

Whatever embarrassment exists might be dissipating, according to Ira D. Sharlip, a urologist and spokesman for the American Urology Association. Sharlip says Viagra has promoted a liberalization in attitudes toward sexuality, and that patients are likely to be more forthcoming regarding ED or other problems now that they know there is a pill that they can take. He suggests that patients, to a large extent, will themselves determine whether they need to take the drug. "Patients are looking for a drug that will improve sexual performance," Sharlip says. "If you are looking to improve your performance, then you have a problem with your performance."

Sharlip says Viagra has been a key catalyst for the formation of a formal area of medical practice called sexual medicine. He says other drugs targeting male performance, including a Johnson & Johnson therapy for premature ejaculation, are in the pipeline, and that the field of female sexual performance is garnering a lot of attention.

The drug has also had an impact in diagnosing other health problems in men. Sharlip says, for example, that an increasing body of literature suggests that ED may be a marker for cardiac disease such as arterial sclerosis. Recently, in fact, FDA approved sildenafil citrate as a therapy for pulmonary hypertension. Viagra has also had the effect of bringing patients into urologists' offices, which is important given the reticence of men to be checked for prostate cancer, according to Sharlip and other physicians.

This would please former Sen. Bob Dole, who, like Nascar's Mark Martin, is a celebrity pitchman for Viagra. Explaining on his website why he added Viagra to the other products he has promoted--such as Pepsi and Dunkin' Donuts--Dole points to his advocacy of early screening, prevention, and treatment of prostate cancer.—RICK MULLIN


The Top Pharmaceuticals
That Changed The World
Vol. 83, Issue 25 (6/20/05)
Table Of Contents

Sildenafil Citrate

Viagra structure


  • 1-{[3-(6,7-Dihydro-1-methyl-7
    sulfonyl}-4-methylpiperazine citrate

CAS Registry

  • 171599-83-0

Other Names

  • Viagra


  • $1.87 billion in 2004

Did you know that Viagra inhibits the enzyme that breaks down cyclic GMP, and that it keeps flowers erect and alive for up to seven days beyond their normal life span?