April 07, 2020

Frog drug becomes human painkiller

WASHINGTON — A deadly poison from the skin of a South American frog provided the decisive clue for the discovery of a powerful new painkiller that 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 . 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 article 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 that 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.

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