In the forests of South and Central America live poison dart frogs. These frogs can carry around toxins 200 times more powerful than morphine. Even small amounts can paralyze or kill other animals. The amount of toxin in only one of these frogs can be enough to kill a large water buffalo or other animals similar in size. These toxins destroy their predators, so how can they be beneficial to humans?
The term “toxin” is defined as a poisonous substance that is produced by living organisms. By definition, toxins are natural. After being amused by the properties of toxins from the poison-dart frog, a team led by Dr. John Daly of the U.S. National Institutes of Health attempted to analyze toxins found in the skin from another frog. In this lab, the scientists found 1 of the 80 toxins in the frogs skin caused mice to arch their tails in a way similar to how they did when exposed to the effects of pain killers. This is how scientists discovered the morphine-like substance they named “epibatidine”. The scientists found that the amount of epibatidine they extracted from the frog (Epipedobates tricolor) was not enough to analyze completely. The team could not obtain any more frogs because they were then declared endangered. Less than one milligram of the rare pain-killer was frozen for keep in their laboratory. About a decade later, chemical methods became available to analyze such small quantities. Epibatidine could one day possibly result in relief for people suffering long-term pain.
The chemistry of natural poisons is an important aspect of their effects. The chemical formula for epibatidine is C11H13N2Cl. Once the chemical structure was found out, scientists discovered how it was closely related to nicotine, which is also a natural chemical compound related to pain relief. After this discovery, many laboratories began synthesizing epibatidine. After these experiments, they realized that epibatidine causes numbness and paralysis. At very high doses epibatidine will cause loss of consciousness, coma and eventually death. However, since it can be deadly even at low doses, it is no longer being researched for potential therapeutic uses because it is too toxic to be used as a pain- relieving drug. But, that made them experiment with the structure to see if they could possibly make another drug that could ease the pain without producing the toxic effects from epibatidine.
With some atomic level rearranging, epibatidine was then changed by medicinal chemists into many new compounds. ABT-594 was one of these new compounds. You can notice the similarity of chemical structures between epibatidine and ABT-594 in the picture below.
ABT-594 then appeared to cause pain relief more effectively than some of the best pain relieving products we have today. After many tests of this new compound, scientists discovered it causes some unwanted side-effects in humans. This made the research continue for another possible epibatidine based chemical compound. Today, new versions of these epibatidine based compounds are currently being tested. At least one of these compounds could in the future possibly be the solution for patients who are suffering long term pain.