Curare
Curare
Curare (pronounced cue-rah’-ree) is a general term for certain chemical substances found in different plants throughout the world’s rainforests. These plants produce a harmless sap which for centuries the natives of the rainforests have refined into a deadly poison. The way of refining and delivering the poison from certain types of plants is similar for natives occupying equatorial regions from South America, Africa, and Southeast Asia. Animals are hunted with blow-guns loaded with darts that have been prepared with lethal doses of the curare preparations.
The word curare is derived from woorari, a word of native American origin from the Amazon and Orinoco basins meaning”poison.“There are different plants used to produce the poisons for the tips of the darts used in hunting. The blowgun is particularly effective against arboreal animals, such as monkeys and birds. The hunters’ final curare preparation is composed of”curares“or poisons from various plants. Curares from these plants share the same chemical composition. They are all alkaloids. An alkaloid is an organic compound containing nitrogen and usually oxygen. They are found in seed plants and are usually colorless and bitter, like codeine or morphine.
The plant Strychnos toxifera produces the strongest type of curare for the hunters of the rainforests. Other curare type plants, however, have been used in western medicine as anesthetics after it was discovered that curares can have nonlethal effects such as skeletal muscle relaxants. Tubocurarine, an anesthetic muscle relaxant introduced into medical practice in the early 1940s contains a curare alkaloid from the chondrodendron plant family.
History
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 systems. 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 patient’s 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
KEY TERMS
Electroconvulsive therapy (ECT)— Formerly known as”shock treatment.“The administration of a low dose electric current to the head in conjunction with muscle relaxants to produce convulsions. A treatment method whose underlying action is still not fully understood, it has proven effective in relieving symptoms of some severe psychiatric disorders for which no other treatment has been effective, for example, severe depression.
Intubation— The insertion of a tube through the throat and trachea as part of the anesthetic procedure using a muscle relaxant. Muscle relaxant—A drug used to relax the voluntary muscles during an operation.
Tubocarine— One of the many muscle relaxants used with curarelike effects.
Ventilation— Keeping air flowing through the lungs after the breathing muscles have been relaxed during an operation.
electro-convulsive 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.
Tubocurarine
Since 1942 there have been about 50 different relaxants used in clinical anesthesia. Tubocurarine, whose chemical structure was determined 1935, is the prototype of a muscle relaxant that still contains the alkaloid constituent of curare and produces a similar physiological effect. Another semisynthetic derivative of tubocurarine is even more potent. It is given intravenously since it is not active when taken orally.
Anesthetic muscle relaxants block nerve impulses between the junctions of the nerve and muscle. It is believed they accomplish this task preventing the acceptance of acetylcholine, which is a chemical neurotransmitter, by the muscle fiber. In addition to the main clinical use of curare is as an accessory drug in surgical anesthesia to obtain relaxation of skeletal muscle, it is also used to facilitate diagnostic procedures, such as laryngoscopy and endoscopy. It is also used in cases of tetanus and myasthenia gravis, an autoimmune disorder.
Resources
BOOKS
Barash, Paul G., Bruce F. Cullen, and Robert K. Stoelting. Clinical Anesthesia. Philadelphia, Lippincott, 1992.
Dripps, Robert D., James E. Eckenhoff, and Leroy D. Vandam. Introduction to Anesthesia. Philadelphia: Saunders, 1988.
Gold, Mark and Michael Boyette. Wonder Drugs: How They Work. New York: Simon & Schuster, 1987.
OTHER
University of California, Los Angeles—Mildred E. Mathias Botanical Garden. ”Curare, a South American Arrow Poison“<http://www.botgard.ucla.edu/html/botanytextbooks/economicbotany/Curare> (accessed November 17, 2006).
Jordan P. Richman