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Beyond Viagra: other phosphodiesterase inhibitors are candidates for potential therapies

The same basic process used by the popular pharmaceutical Viagra may someday help people suffering from a variety of conditions, from allergies to diabetes. Viagras success has raised interest in the growing study of phosphodiesterase (PDE) inhibitors, says Joseph Beavo, Ph.D., a professor of pharmacology at the University of Washington School of Medicine.

Viagra works by inhibiting one specific type of enzyme called a cyclic GMP phosphodiesterase. "There is not just one, but many phosphodiesterases. Different PDEs are expressed in different tissues and in different parts of the cell, and have different physiological functions. 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," Beavo says.

Beavo discussed PDEs and their inhibitors during the "Signal Transduction" panel at the American Association for the Advancement of Science annual meeting here today.

The different PDEs make up a large class of enzymes. Beavo and his colleagues discovered many of the 11 families that are recognized so far. These enzymes are found throughout the body, where they modulate many important functions. For example, they play a key role in many sensory processes including vision and smell. They may even play a role in learning and memory. On the one hand, this means that drugs regulating PDEs may someday provide a treatment for people with vision or memory problems. But at the same time, any researcher wanting to use PDE inhibitors to treat one specific part of the body must make sure that the therapy does not interfere with other PDEs such as the ones involved in vision or memory.

Most PDE inhibitors currently available as medication affect PDEs in multiple organs, and so their use is often limited by their toxic side effects. Viagra, introduced in 1999, became a poster child for PDE research in part because of its selectivit
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Contact: Walter Neary
wneary@u.washington.edu
206-484-1384
University of Washington
16-Feb-2001


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