A toxin derived from the skin of a South American frog led to a potential new pain reliever that may lack some of the side effects of morphine. In tests on animals, the drug, which apparently is not opioid receptors but rather by a receptor for the neurotransmitter acetylcholine, has proved effective in blocking the acute and chronic pain. In addition, the researchers saw little evidence that the drug, reported in Science today is addictive or toxic.
The drug's design was based on a compound extracted from the skin of an Ecuadorian frog by chemist John Daly, of the National Institute of Diabetes and Digestive and Kidney Diseases. In 1976, he discovered that the compound, called epibatidine, is 0 times more potent than morphine in blocking pain in mice. Unfortunately, it also caused convulsions and even death. Approximately 10 years later, her lab used nuclear magnetic resonance spectroscopy to determine the structure that resembles epibatidine to that of nicotine. Other experiments have shown that the compound activates the nicotinic acetylcholine receptor.
The research has attracted the attention of a team from Abbott Laboratories Abbott Park, Illinois, who noticed that the epibatidine structure resembles that of the compounds they studied as therapies for Alzheimer ' Alzheimer. Neuropharmacologist Stephen Arneric and colleagues fiddled with their compounds, trying to create a derivative that only kills the pain.
They have now shown that a variant, called ABT-594 is as effective as morphine in acute and chronic pain wetting rats. By placing electrodes in the spinal cord of rats, the researchers also showed that the drug inhibits the ability of nerve cells to fire in response to noxious mechanical and thermal stimuli, but it does not affect the touch response or the gentle heat. The company also found Arneric said that ABT-594 depresses the respiratory system less than morphine does, and it makes the animals more alert instead of the sedative. In addition, in at least one test, ABT-594 appears to be nonaddictive.
Much more work will be needed to determine whether the drug is safe and effective in humans. For example, other researchers point out that ABT-594 mechanism of action raises the possibility that it will lead to other forms of addiction. Abbott has begun safety testing in Europe and hopes to conduct trials in this country as well. "If it works in people, it'll be a whole new kind of pain," said Howard Fields, professor of physiology and neurology at the University of California, San Francisco.
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