|
|
EXIT MORPHINE
A new painkiller from frog
skin is on its way, reports Biplab Das
A new drug derived from a toxin found in the skin of frog species may prove to be an effective pain reliever that does not cause the harmful side effects associated with morphine-derivatives.
Morphine's monarchy as a painkiller has not been without its negative effects. Its addictive properties and side effects such as respiratory depression have caused doctors and patients to shy away from it.
Now, animal tests have shown promising results with ABT-594, a drug derived from frog skin by a research team comprising Stephen
Arneric, Michael Decker and Mark Holladay of Abbott Laboratories in Abbott Park, Illinois.
Through experiments conducted on rats, the researchers found that ABT-594 acts on a receptor for the neurotransmitter,
acetylcholine, instead of the usual opioid receptors. "If it works in people, it is going to be a completely new kind of pain reliever," says Howard Fields, professor of physiology and neurology at the University of California, San Francisco. Abbott has begun safety trials of the drug in Europe.
In 1932, researchers got the first clue on blocking pain by targeting the acetylcholine receptor using nicotine. In the'90s, John Daly of the National Institute of Diabetes and Digestive and Kidney Diseases detected a compound in the skin of a frog that had been collected from
Equador. Daly noticed a surprising result when he injected the compound in mice. The animal's tail stood up and arched over its back.
This intrigued Daly who knew of many opioids that triggered a similar response. "I still remember looking at the mice and getting excited," says Daly. The compound was named after the frog,
Epipedobates tricolor. Even in the presence of opioid inhibitors, epibatidine remained effective, which indicated that it worked through different receptors. After knowing the compound's structure, Daly's group showed that epibatidine activates the nicotine acetylcholine receptor. However, epibatidine is toxic for humans. Even in lab animals, it is known to cause seizures.
The research team at Abbott Laboratories wanted to create an
epibatidine-derivative to overcome the toxicity problem. They produced 500 variants of
epibatidine. Among these, ABT-594 was tried out by the researchers to combat different types of pain.
To test the drug, the scientists compressed a nerve in the spinal chord of a rat through surgical means and then applied different degrees of pressure on its paw. In this case, the drug could alleviate pain just as well as morphine. In another experiment, it was found that the drug hinders the ability of nerve cells to respond to harmful mechanical and thermal stimuli exempting responses to benign sensations such as touch or mild heat.
Reporting their work in a recent issue of Science, the scientists wrote that ABT-594 binds to acetylcholine receptors more efficiently than
epibatidine. "They came upon a compound that gets rid of the toxic effects of epibatidine and still has analgesic capabilities," says Daly. If the drug is found safe and effective for humans, it could well be the ideal painkiller of the future.
|
|
