JUMPING RATS | Frogs to Fags

Discovery and Developments

Jumping rats

A history of Epibatidine

Dr. John Daly

   Frogs of the Dendrobatid family live in South American families and produce some of the dealiest natural poisons known. One of the 165 species in this family happens to be Epipedobates Tricolor from which epibatidine was extracted.

200 times more effective at pain suppression than morphine, Epibatidine was isolated by John Daly in 1974. Dr. John Daly worked for the National Institute of Health and his research group extracted the poison from the Equadorian dart frogs and tested them for painkilling activity.

This was performed by the hotplate test, where a rat is placed on a heated plate, and if the rat is not injected with analgesic, it will jump up from the pain.

Even on injection of 5 microgram (1mcg=1 millionth of a gram) of epibatidine, the rat would not jump, proving that epibatidine was 200 times more effective than morphine. Even when injected with naloxone, a drug negating the effect of morphine, the rat would not jump, showing epibatidine operates on a different pathway from opioids.


  Tragically, 750 frogs had to be killed to produce just 60mg for analysis, so that with this one off sacrifice, artificial synthetic routes could be devised. Even so, at the time, without the aid of spectroscopic methods, the structure could not be deduced.

Equador did not allow more frogs to be taken from the rainforest, and as such small amounts were extracted from each frog, (a tenth of a milligram), an attempt was made to breed the frogs in captivity. This failed, as it was discovered that the captive frogs produced no epibatidine, leading the researchers to conclude that the alkaloid was derived from the frog's diet and environment. With no new source of epibatidine, and the remaining amount insufficient for further research, the sample was stored away for over a decade.

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