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Poison from frog leads researchers to new painkiller
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WASHINGTON (January 1, 1998 7:30 p.m. EST) -- A deadly poison from the skin of
a South American frog provided the key to a powerful new painkiller
researchers say may have all of the benefits of morphine, but none of the
damaging side effects.

Researchers at Abbott Laboratories in North Chicago, Ill., developed the new
painkiller, called ABT-594, after scientists at the National Institutes of
Health isolated a poison from the skin of an Ecuadorian frog called
Epibpedobates tricolor.

John Daly of the National Institute of Diabetes and Digestive and Kidney
Diseases, a NIH agency, found in 1976 that an extract from the frog's skin
could block pain 200 times more effectively than morphine. He called the
compound epibatidine in honor of the frog.

Although epibatidine appeared to be a painkiller in rats, it was too toxic to
use in humans.

Ten years later, NIH researchers used new analytic tools to determine the
chemical structure of epibatidine and found that it resembled nicotine. This
was consistent with its painkilling effect.

Scientists had known for decades that nicotine in the blood would attach to a
nerve cell and produce a mild analgesic effect.

A brief report on the compound, along with a diagram of its chemical
structure, was published in the journal Science.

Researchers at Abbott realized that the chemical structure was close to a
group of
experimental drugs that the company was testing for treatment of Alzheimer's
disease.

They also worked on the nicotine receptors on nerve cells.

"Chance favors the prepared mind," said Michael Williams, a scientist and vice
president at Abbott.

"We had a slew of compounds that we knew interacted (with the nicotine
receptors). We then looked through them for some that had analgesic
potential."

After screening some 500 compounds, the Abbott researchers selected the drug
ABT-594 for further testing.

Its chemical structure closely resembled epibatidine, but it lacked the
elements that made the frog compound toxic.

"The frog didn't make epibatidine for the benefit of humans, but rather to
kill predators," said Williams.

"We needed to get rid of the (poisons) that affected the cardiovascular system
and the respiratory system."

In a research to be published Friday in Science, Williams and his colleagues
report that in laboratory animals studies, ABT-594 appears to be many times
more powerful than morphine, but it lacks the serious side effects of that
drug.

And right now, morphine is the main drug used for treatment for intense and
unrelenting pain, such as from cancer or injury.

According to Science, there are 30 million to 40 million Americans with
moderate to severe pain that is not affected by common analgesics, such as
aspirin or ibuprofen.

And there are thousands with chronic pain who depend on morphine, despite its
side effects, just to get through the day.

Williams said that morphine can suppress breathing. This means the drug often
cannot be used to control pain in patients who already have respiratory
problems.

Morphine also can stop the digestive movement inside the intestines and bowel,
which can lead to dangerous constipation.

Williams said that the condition can become so serious that some patients will
stop taking morphine and endure their pain to avoid constipation.

The effectiveness of morphine also declines from chronic use and can become
addictive.

Williams said that tests with laboratory animals showed that ABT-594 does not
diminish respiration nor cause constipation.

He said laboratory animals also showed no sign of addiction to ABT-594 and the
drug appeared to be effective no matter how long it was used.

The drug is now in early human safety testing in Europe and the results should
be known by the summer, said Williams.

Many in the medical field say there is an urgent need for new drugs against
pain.

"If it works in people, it's going to be a completely new kind of pain
reliever, Howard Fields, a professor of neurology at the University of
California, San Francisco, said in Science.


By PAUL RECER, The Associated Press
Copyright 1998 Nando.net
Copyright 1998 The Associated Press
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janet paterson / 50-9 / [log in to unmask]