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Take One Snail And Call Me In The Morning...continued

One Frog's Poison

John Daly had a problem. True, he had harvested an intriguing chemical from the skin of an Ecuadorian tree frog Epipedobates tricolor, and true, the chemical, called epibatidine, was at least 200 times more potent than morphine as a pain killer in animals. But Daly, a researcher at the National Institute of Diabetes and Digestive and Kidney Diseases, wanted to make epibatidine in quantity, and to do that he needed to know the chemical’s shape -- its structure. To determine the structure on his mid-1970’s machines, he needed more of the chemical.

Ecuadorean Tree Frog

Unfortunately the frog was now on the endangered species list, so more collecting was out. As for laboratory-grown frogs, they didn’t seem to make the chemical, probably because a bug that supplied the crucial chemical precursor was lacking from their diet. Daly sat on his precious but insufficient supply of epibatidine, waiting for technology to catch up with him.

In the 1980s, help came in the form of more sensitive nuclear magnetic resonance (NMR) machines, which Daly used to determine the structure of epibatidine. Several groups then made synthetic epibatidine.

But there were more problems. Epibatidine was potent against pain, but it was also potent in some unwanted directions -- it caused high blood pressure, paralysis, and seizures. Daly found that it acted by hitting a particular kind of protein on a nerve cell called the nicotinic acetylcholine receptor (nAChR). The nAChR is the receiver in the nerve-cell relay race: it detects the presence of the chemical messenger acetylcholine, which is released by one nerve cell, and relays that message to the next nerve cell. Acetylcholine, epibatidine, and the nicotine found in cigarettes can all turn on the nAChR.


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