Viagra's Enzyme Action May Give Pfizer Schizophrenia Advance

(September 21, 2006) -- Viagra has improved sex for millions of men and has generated $12 billion in sales for Pfizer Inc. Now the erection pill is providing the world's biggest drugmaker clues to a new way to fight schizophrenia.

Researchers at Pfizer are using insights into Viagra to design experimental drugs that may improve on Zyprexa, the best- selling schizophrenia remedy from Eli Lilly & Co., with $4.2 billion in sales last year. Viagra causes an erection by turning off an enzyme in the body. Blocking similar chemicals in the brain may silence the hallucinations typical of schizophrenia, the researchers say.

A better schizophrenia drug would be a boon for New York- based Pfizer and the 2.5 million Americans who suffer the debilitating mental disorder. Pfizer's current schizophrenia medicine, Geodon, had only 4 percent of the $15 billion spent worldwide in 2005 for anti-psychotic drugs. Researchers say the new Viagra-like compounds will be developed only if shown in human tests to be safer and more effective than existing drugs.

``We believe this drug is going to be different,'' says Frank Menniti, a scientist at Pfizer's Groton, Connecticut, labs. ``Our job isn't just to make another anti-psychotic. We need to make a better anti-psychotic than what is out there.''

Starting in 1998, company researchers began probing the role that a family of enzymes called phosphodiesterases play in the human body, says Martin Jefson, a Pfizer scientist. Viagra works by inhibiting one of the enzymes in the group. The scientists figured drugs similar to Viagra that block other forms of the enzyme might be useful in other diseases, according to Jefson.

Mapping Enzymes

Within a year and a half, the Pfizer team had mapped the location in the body of all the enzymes, including one in the brain linked to mental illnesses such as schizophrenia and obsessive-compulsive disorder, Menniti says.

In late 1999, a research team at Pfizer's Sandwich, England, labs began making gallons of the schizophrenia-related enzyme from insect cells. With plenty of the enzyme on hand, the scientists tested thousands of chemical compounds during the next four years to see whether any blocked the enzyme's activity in test-tube experiments, says Menniti.

Chemists then adjusted the structure of compounds that showed some action against the enzyme to make a molecule most likely to be safe and effective in humans, Jefson says. By 2003, after researchers had synthesized a batch of chemicals that impeded the brain enzyme, they began testing the compounds' effects in lab animals, he says.

Human trials are probably years away, and there is no certainty that the U.S. Food and Drug Administration will be able to measure the mood enhancements that Pfizer envisions. The agency may not be able to approve drug for that benefit.

Hearing Voices

Schizophrenia, which usually strikes people in their teens to late 20s, causes victims to hear voices, feel frightened and hallucinate, all of which makes leading a normal life impossible, doctors say. As many as one in 100 people in the U.S. may be victims of the disease, according to the National Institute of Mental Health in Bethesda, Maryland.

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The most popular drugs, such as Zyprexa, from Indianapolis- based Lilly, and Risperdal from New Brunswick, New Jersey-based Johnson & Johnson, and three other similar drugs including Pfizer's Geodon, allow many with the disease to live symptom- free. Still, some patients don't regularly take their pills, and about 74 percent stop treatment after 18 months, according to a 2005 study in the New England Journal of Medicine.

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Last updated: 09/06

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