When Viagra was introduced in 1999, it became a household word seemingly overnight. Since then, its potent effect on erectile dysfunction has made it one of the most widely prescribed drugs. Viagra, however, is only one member of a class of agents known as phosphodiesterase inhibitors, and the success of the little blue pill has raised considerable interest in the potential of its classmates to combat a variety of other conditions. Joseph Beavo of the University of Washington discussed these prospects on Saturday at the annual meeting of the American Association for the Advancement of Science in San Francisco.

Viagra inhibits a type of enzyme found in the penis called a cyclic GMP phosphodiesterase (PDE). But there are many kinds of PDEs, Beavo explains. In fact, 11 families of the enzymes are known so far. PDEs play an important role in sensory processes, including vision and smell, and they may likewise contribute to learning and memory. Research conducted in Beavo's lab has also identified PDEs that appear to mediate immune system activity. Scientists are thus investigating whether inhibiting these enzymes might help control anti-immune and hyperinflammatory diseases, such as rheumatoid arthritis and allergies. Other PDEs are involved in insulin secretion and leptin signaling, and so might be good targets in treating diabetes and obesity.

"Different PDEs are expressed in different tissues and in different parts of the cell, and have different physiological functions," Beavo explains. "The challenge has been for the drug companies to find agents that are selective for specific phosphodiesterases so that they can treat the disease without causing toxic side effects." Yet because a number of PDEs have been discovered within the past year, the search for those with Viagra-like specificity has only just begun. In the future, PDEs could even be used to enhance memory and to treat chronic obstructive pulmonary disease and blood clotting disorders. But much research and testing will be needed before any of these visions come to pass.

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