The Discovery of Epibatidine

 
 
 

photo compliments of
Dr. Shin Sugiyama
 
 
 
 
 
 
 
 

Introduction

History

Cellular 
Mechanism

Medicinal 
Applications

Legends 
and Folklore

References
 
 
 
 
 
 
 
 
 
 
 
 

 

     John Daly, a researcher for the National Institute of Health, was the first to conduct an intensive study on the Epipedobates tricolor.  Daly and his associates began to collect poison dart frogs from the Ecuadorian highlands in 1974.  It was during one of their first missions to South America that Daly and his fellow researcher, Charles Myers, of the American Museum of Natural History, realized the true danger that the toxic secretions posed.  Although Myers and Daly took great precautions when conducting their research, always wearing protective clothing and taking care to burn the protective gear immediately after contamination with the toxin, the scientists were not confronted with its true power until they woke up one morning to find the bodies of several animals near the area where their clothes had been burned the night before. (Bainbridge, 1989) They concluded that the deaths of these animals had resulted from the ingestion of the frog toxin that remained  This event led Daly to pronounce that the potency of the “secretions made strychnine look like table salt” (Bainbridge, 1989).  Even in the wake of this occurrence, and the associated knowledge that it elucidated, the first studies conducted on Epipedobates tricolor and several other species of poison dart frogs were extremely primitive and especially risky.  In an effort to determine the relative virulence of the toxins emitted by various species the scientists agitated the frogs, causing them to secrete the toxin, and then touched the frogs skin with their tongues.  The observations recorded in the study indicate that species of mild toxicity produced a bitter taste, followed closely by numbness of the tongue and tightening in the throat (Bainbridge, 1989).  This method could not be used with all species of frogs, however, because the more deadly species - such as the Phyllobates terribilis - can secrete enough poison to bring about the deaths of multiple humans (Bainbridge, 1989). This simple test was not as dangerous as it may seem, though, for most dart frog toxins are only deadly upon entering the bloodstream (Turkington, 1999).  However, the most potent toxins do quickly give rise to significant irritation, including blistering and swelling (Turkington, 1999).

Photo compliments of Jesper Hansen
http://hjem.get2net.dk/jesper_hansen2/epipedob.html
 

     Upon returning to the United States with their sample species, Daly and his coworkers determined that the secretions contained an alkaloid material which elicited a straub-tail response - the raising and arching of the tail in mice injected with the substance - characteristic of opiods (Strong, 1998).  Shortly after this discovery, Daly was forced to stop his research, for a period of more than ten years, due to the introduction of an international treaty banning the collection of the Epipedobates tricolor  (Strong, 1998).   During this ban, Daly attempted to raise the frogs in captivity.  Unfortunately, he soon realized that the secretions rapidly lost their analgesic effects and formed the hypothesis that the poison resulted as a byproduct of some indigenous substance ingested in the wild (Moffet, 1995).  The actual substance was not determined until 1997 when Daly and other NIH researchers released the finding that the frogs build up high levels of the alkaloid in their skin by eating a huge number of ants, which also contain the deadly chemicals in small amounts.  The more ants eaten by the frogs, the greater the amount of alkaloid present in their skin and the greater their overall toxicity. (Current Science, 1997) 
 
 
 

Photo compliments of Reto Siegenthaler

 
 
This website was created for a biology course entitled "From Venoms and Toxins to Drugs" at  College in Davidson, North Carolina.  All questions and/or comments should be directed to Amy Johnston.