Mechanism of Action

The collaborative project of Benjamin Brodie (1783–1862) ( Fig. 1-12A ) and Charles Waterton (1783–1865) (see Fig. 1-12B ) initiated our modern understanding of muscle relaxants.^[327] Benjamin Brodie was the principal figure of English surgery at that time, and Waterton was the eccentric Squire of Walton Hall, near Wakefield, England. Waterton had traveled extensively, including several expeditions into British Guiana, where he owned property and eventually obtained several samples of the arrow poison.

In 1814, Brodie and Waterton^[328] demonstrated that an animal could survive a curare injection provided that ventilation was continued after injection. For this famous experiment, it seems that Waterton supplied the curare and the animal—a donkey—and Brodie supplied the experimental idea. They injected the donkey with poison in the shoulder, and it was immobilized within 10 minutes.

An incision was then made in its windpipe, and through it the lungs were inflated for two hours, with a pair of bellows. The ass held up her head, and looked around, but the inflating being discontinued, she sunk once more in apparent death. The artificial respiration was immediately recommenced and continued without intermission for two hours. This saved the ass from final dissolution: she rose up and walked about; she seemed neither in agitation nor pain.

Waterton named the donkey Wouralia and nurtured her on his estate, where she died 25 years later. Curiously, in their later correspondence, neither partner mentions the collaboration of the other individual. Waterton's book,^[328] entitled Wanderings in South America and dated 1879, contains an extensive description of the preparation and use of curare, as well as the manner of use of the blowpipe, which he called the "extraordinary tube of death."

The experiment performed by Claude Bernard^[329] (1813–1878) demonstrating the action of curare at the junction between the nerve and muscle was deceptively simple ( Fig. 1-13 ). In his studies with curare, Bernard used the drug to open up a new area of investigation, the physiology and pharmacology of the junction between the nerve and muscle. Experiments on the specialized apparatus where the action of curare is primarily located, the neuromuscular junction, were begun by one of Bernard's students, Willy Kuhne^[330] (1837–1900).