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Deriving a non-opiate painkiller [ABT-594] from Epipedobates tricolor



Toxics produced by poison arrow frogs have applications for human health. In 1974, John Daly of the National Institutes of Health collected samples of skin secretions from Epipedobates tricolor, an orange, red, and white frog from Southwestern Ecuador. Studies found that small amounts of the dendrobatid toxin administered to mice worked as an nonaddictive painkiller that blocked pain 200 times more effectively than morphine. Daly named the new compound epidatidine in honor of the frog. Unfortunately further testing found epidatidine to be too toxic for use in humans. In order to produce a potent, but less toxic version of the molecule, a larger sample of epidatidine would be required. Mark Plotkin describes Daly's return expedition to Ecuador in Medicine Quest [2000]:
    The original epidatidine had been extracted from frogs collected from two different locales in 1974. When the scientists returned to Ecuador two years later, one population of the amphibians had completely vanished; much of the surrounding forest had been felled and converted to banana plantations. Fortunately, they were able to find these frogs at the other site—but only enough to collect less than one milligram of the poison! Then, in 1984, passage of the Convention of International Trade in Endangered Species (CITES) Treaty made it exceedingly difficult (if not impossible) to legally collect and export poison arrow frogs, particularly in the large quantities necessary for chemical analysis of the toxin. And habitat destruction in western Ecuador was on the increase. Attempts to breed the frogs in the lab were successful, but the frogs contained no epidatidine! So Daly had a tiny and finite supply of epidatidine, and demand for the compound for testing purposes was increasing. Daly stored his precious poison, awaiting the day when modern technology would improve to the point of being able to unlock one of Mother Nature's most closely guarded (and potentially useful) secrets.
By 1990 technological breakthroughs allowed Daly to unfreeze his single epidatidine sample and submit it for analysis. Within two years the molecule structure (similar to nicotine) was unmasked, and scientists were able to synthesize epidatidine for experimentation. Abbott Laboratories began working with epidatidine in an effort to develop similar compounds with applications for treating pain in humans. Abbott Labs eventually created ABT-594, a non-toxic, nonaddictive painkiller potentially effective for treating several types of pain. Unlike an opiate, ABT-594 "promotes alertness instead of sleepiness and has no side effects on respiration or digestion" [Wilson 2002].

Back to Floor Reptiles and Amphibians.

References and other resources:
http://www.abdn.ac.uk/chemistry/abt/ - ABT-594 structure, characteristics. Picture of Epipedobates tricolor.
Bannon, A.W. Journal of Science. 1998, Jan, 279, 77-81.
Holladay, Mar W. J.Med Chem. 1998, Feb, 41, 407-417.
Plotkin, M.J. Medicine Quest. 2000. New York: Viking Penguin. 3-6.
Wilson, E.O. The Future of Life. 2002. New York: Alfred A. Knopf. 121-122.





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