Curare

Early eighteenth and nineteenth century researchers studied the effects of curare. In 1780 Abbe Felix Fontana found that its action was not on the nerves and heart but on the ability of the voluntary muscles to respond to stimuli. In British experiments, several English researchers showed that animals injected with curare would recover if their respiration was artificially continued. Laboratory experiments were continued throughout the nineteenth century using curare to find out more about the relationship between the nervous and skeletal muscle system. In 1850 Claude Bernard using curare identified the neuromuscular junction where the curare interferes with the acceptance of the neural impulse. Earlier in that century Squire Waterton had conjectured that curare could be used in the treatment of tetanus.

The first use of curare in surgery was in 1912. A German physician and physiologist, Arthur Lawen, wrote about his use of curare in surgery on a patient. He was able to relax the patients abdominal muscles with a small amount of regular anesthesia after administering curare. In order to control the curare he also learned how to intubate (insert a tube into the patient's trachea) and then ventilate the lungs, that is add air through the tube to control breathing. His reports, which were published only in German, were ignored largely because anesthesiologists at that time had not learned the techniques of intubation and ventilation.

In 1938 Richard and Ruth Gill returned from a trip to South America to New York with a large stock of crude curare. They collected these plants from their Ecuadorian ranch for the Merck Company. At that time there was some interest in using curare for the treatment of a friend who had multiple sclerosis. Merck lost interest in the project, but some of the Gill's curare stock passed on to Squibb & Co. Early use of the drug for anesthetic purposes, however, were not successful, and interest was dropped at that time for further clinical experimentation.

Interest in curare resumed in 1939 when psychiatrists from the American midwest began to use it to treat certain categories of patients. Children with spastic disorders were injected with curare but when no long range improvement was observed, these psychiatric researchers passed it on to those who were using Metrazol, a drug that was a precursor to electroconvulsive therapy (ECT), formerly referred to as shock treatment. The curare appeared to absorb some of the intense muscle responses or seizures, thus helping to avoid seizure induced fractures to the bones. Other psychiatrists began to experiment with the drug after its successful application to ECT.

Shortly afterwards a Canadian physician, Harold Griffith, began to prepare to use curare for surgery after he saw the positive results of its use in psychiatric patients. He first utilized curare in an operation on January 23, 1942. Then he reported on the successful use of curare as a muscle relaxant for this operation, which was an appendectomy. He administered the curare after the patient's trachea was anesthetized and intubated early in the operation. The muscles of the abdominal wall became relaxed by the curare to help in the performance of the operation. Twenty-five other patients received similar treatment. After Griffith's report of his work, the use of curare and other synthetic type curare muscle relaxants became the standard practice for surgical procedures requiring muscle relaxation.