Interacting amino acid replacements allow poison frogs to evolve epibatidine
" patent, however, is still valid despite evidence that the product was developed using 750 tricolor poison frogs smuggled out of Ecuador.
From a cocktail of compounds taken from the backs of the frogs, Daly and his fellow chemists isolated and characterized the toxin itself, a molecule resembling nicotine, which they named epibatidine. This natural product proved 200 times more effective in the suppression of pain than opium, but was also too toxic, unfortunately, for practical use.
The destruction of much of the habitat in which populations of Epipedobates live almost prevented the discovery of epibatidine and its synthetic analogues.
Several years ago, a research team led by John Daly of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., found that the frog skin toxin epibatidine, an analgesic hundreds of time more potent than morphine (SN: 7/18/92, p.
Nonetheless, epibatidine inspired the investigators at Abbott to explore whether some of the nicotine analogs being developed by the company for other medical purposes might equal the frog toxin's analgesic prowess--but not its toxicity.
One alkaloid, called epibatidine, numbs more effectively than morphine, and several others show promise as heart attack medicines.
It took a decade, but this spring, he and his colleagues described the structure of epibatidine in the April 22 Journal Of The American Chemical Society.
So by measuring the amount of absorption of each wavelength and comparing those data with absorption data from known compounds, Daly concluded that in one part of the epibatidine molecule, a ring with three double bonds connected five carbon atoms and one nitrogen atom.
They exposed it to a compound called acetic anhydride, which reacted only with the nitrogen in epibatidine, changing it slightly so it could be separated from the sample's impurities.
It turns out that the other nitrogen atom, which exists in the ring of the second fragment, made it difficult for chemists to get plain epibatidine. Pharmacologists need this plain form so they can study the compound's therapeutic potential.