New Drug Is Nitroglycerine Without Downside

Heart failure compound has benefits, no side effects in dogs

MONDAY, April 14, 2003 (HealthDayNews) -- A new kind of drug that appears to have all the benefits of nitroglycerine in treating heart failure but none of its deficiencies looks good in animal tests, researchers report.

The discovery is a marvelous example of how scientific discovery works -- one brick on top of another, with some luck thrown in, says Dr. David A. Kass, a professor of medicine and biomedical engineering at Johns Hopkins Medical Institutions and lead author of a paper on the research in the April 14-18 issue of the Proceedings of the National Academy of Sciences.

It starts a little more than a decade ago with the discovery of how nitroglycerine, which has been used to treat heart failure for a century or more, actually works: by releasing a chemical called nitric oxide in the body. That discovery led to nitric oxide being named "molecule of the year" in 1990.

But nitroglycerine has its downside. While it helps a weakened heart get blood to the body by widening blood vessels, it also blunts the beta-adrenergic system that powers the heart's contractions. "It's like having your foot on the brake when you're driving," Kass explains. The new compound doesn't have that defect.

Two years ago, Kass talked with Dr. David Wink, a researcher at the National Cancer Institute, who had been doing some work with nitroxyl anion, a molecule of nitric oxide with one electron added. Wink's work indicated that nitroxyl anion might damage the heart, but Kass and Wink thought it looked interesting enough to warrant a closer look. "I handed it to one of my postdoctoral students, a little like a fishing expedition," Kass says.

They caught a big one. Nitroxyl anion not only widens blood vessels but strengthens the force of heart's contractions, lab work showed. Dr. Nazareno Paolocci, a scientist in Kass's group, took over, pushing the studies to see whether that effect could be put to medical use.

It looks very good, the journal report says. When a compound called Angelis' salt that produces nitroxyl anion in the body was given to dogs with congestive heart failure, not only did their blood vessels widen but the force of their hearts' contraction nearly doubled.

There is great promise in the research, says Martin Feelisch, a professor of physiology at the Louisiana State University Health Sciences Center who wrote an accompanying editorial. "What is new here is the appreciation that a very primitive molecule, nitric oxide with just one electron more, has completely different properties."

The compound used in the study "is not the breakthrough drug that will make it through to clinical trials," Feelisch says. "But the trial does show that with this principle, it is possible to come up with a new pharmacological way to improve the contractability of the heart."

Angelis' salt isn't the breakthrough compound, Kass agrees, and research has quickly moved beyond it. His laboratory has developed "a completely new nitroxyl anion donor that is almost 100 percent effective" and could eventually result in a simple pill for people with heart failure. He doesn't want to name the molecule, but steps have already been taken to patent it, and there have been "preliminary discussions" with one pharmaceutical company about the lengthy series of tests needed to bring a drug to market, he says.

Kass hopes to get more of a response from the pharmaceutical industry. "With this data published, we are interested in seeing what shakes out," he says.

More information

You can learn about heart failure and its treatment from the American Heart Association or the National Heart, Lung, and Blood Institute.

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