Curare

I first came across the drug Curare in the Yelena Zaltana series of books by Maria V Snyder. The drug runs through the book series as a method used for both good and evil, as a relaxant for various procedures and also as a poison. Although I knew that curare was a real thing,  I was unaware when I first read the series just how accurate her use of Curare is. We covered the drug in detail in my Introduction to Toxicology lectures, and I thought I could share that knowledge here:

Curare is a resin obtained from the bark of South American trees of the genera Strychnos and Chondrodendron that causes paralysis of voluntary muscle. It acts by blocking the action of the neurotransmitter acetylcholine at neuromuscular junctions. The name curare is derived from the native Guyana Mukusi Indian word Wurari or Woorari. it is now called d-tubocurarine or just curare. Its use originates from South American natives coating blow dart tips with the resin and using it in hunting. The poison paralyses and kills prey, while not preventing them from being eaten, as curare has no effect when consumed. It has to enter the bloodstream directly.

A Brief Timeline – some of these dates are debated.

• There is no written record of when curare was first extracted and used on blowdarts. However, we know that the process was perfected and in common use well before the first encounters with explorers.
• In 1596 Sir Walter Raleigh referenced a substance that is now thought to be Curare in his book ‘ The Discovery of the Large, Rich, and Beautiful Empire of Guiana‘, where he talks of the poisoned arrows shot by natives at the invading parties. He was curious to identify the poison but did not detail anything, he may have brought specimens back of this substance.
• In 1780, Abbe Felix Fontana identified the action of curare on voluntary muscles, instead of acting on the heart and nerves as previously thought.
• In 1800, Alexander von Humboldt described the extraction of curare from vines/lianas.
• In 1811, Sir Benjamin Collins Brodie determined that complete recovery from curare poisoning is possible provided artificial ventilation/ breathing is maintained.
•  In 1825 Curare was first brought to Britain by Charles Waterton, Squire of Walton Hall. Waterton is chiefly remembered for his association with curare, and for his writings on natural history and conservation. David Attenborough has described him as “one of the first people anywhere to recognise, not only that the natural world was of great importance, but that it needed protection as humanity made more and more demands on it”.  Waterton injected a donkey with curare and then using a pair of blacksmiths bellows he kept the animal breathing artificially until the curare finished acting.
• In 1835 Sir Robert Hermann Schomburgk classified and named the vine Strychnos toxifera.
• In 1850, George Harley demonstrated that curare could be used to treat tetanus and strychnine (a common rat/pest poison) poisoning.
• By 1868, Claude Bernard and Alfred Vulpian had identified the site of action of curare as the motor endplate.
• From 1887, curare was marketed for medical use by Burroughs Welcome.
• In 1900, Jacob Pal recognized that physostigmine could be used to antagonize the effects of curare.
• In 1912, Arthur Lawen demonstrated the use of curare during surgery, but this potential was not realized as the finding was published in German.
• In 1935, Harold King isolated d-tubocurarine and described its structure (as a crystalline alkaloid) and continued to study it for 13 years, publishing at least 10 papers on the subject.
• In 1936 Dale revealed the role of acetylcholine in neuromuscular transmission and the mechanism of action for curare.
• In 1938 Richard C. Gill brought enough crude curare paste back to America to perform human studies, Some American accounts credit Gill with the introduction of curare to western medicine, though you can see from this timeline that that introduction happened almost 400 years earlier. However, Gill was a big part of introducing Curare to the US.
• In 1940, Abram Elting Bennett revealed that curare could be used to reduce trauma during metrazol-induced convulsive therapy for spastic disorders in children.
• In 1942, Harold Griffith and Enid Johnson used curare to augment general anaesthesia when performing an appendectomy. 
• Curare was used surgically until the development of safer synthetic neuromuscular blocking analogues such as Pancuronium (in 1964), Vecuronium (in 1979), Mivacurium (in 1993), and Rocuronium (in 1994).

References:

S.A. Burr and Y.L. Leung, Curare (D-Tubocurarine), Encyclopedia of Toxicology, 2014, pages 1088-1089

T.C. Gray, Harold King, Anaesthesia, 199 1, Volume 46, pages 679-682

A.E. Bennett, The History of the Introduction of Curare into Medicine. Anesthesia & Analgesia. 1968 – Volume 47 – Issue 5 – p 484-492

Curare – an overview, Science Direct, https://www.sciencedirect.com/topics/neuroscience/curare