Curare

Curare is a name used to identify a variety of highly toxic (poisonous) extracts from some types of woody vines that grow in South America. European scientists began studying curare in the late sixteenth century after explorers learned that Indians living along the Amazon and Orinoco Rivers in South America had been using it for centuries to make poison-tipped hunting arrows. The poison in the arrows killed animals by paralyzing (numbing) their muscles. When the muscles used for breathing became paralyzed, the animals died of suffocation. These deadly arrows were sometimes used against the European explorers and soldiers. Natives called the poisonous plant ourari (or "woorari"), which became "curare" to the Europeans.

In 1735 a scientific expedition sponsored by the French Academy of Sciences was sent to the area of South America that is now Ecuador. Heading the expedition was the Frenchman Charles Marie de la Condamine, who spent part of ten years in South America scientifically exploring the region. La Condamine collected samples of curare and took them back to France.

During the nineteenth century, doctors tried to use curare as a muscle relaxant in the treatment of rabies, tetanus (an infectious disease that usually enters the body through a wound), and epilepsy (a chronic, or lasting, disease of the nervous system characterized by convulsions), but these trials were unsuccessful because available curare extracts were not of equal quality and potency (strength). In the 1870s curare was used to keep conscious animals from moving during experimental surgery. This practice angered many people in Great Britain and led to the passage of anti-vivisection laws (laws against using animals for scientific experimentation).

The first breakthrough leading to successful medical use of curare came in 1935, when Harold King isolated its active principle, which he called tubocurarine. A chemically pure alkaloid (an organic base of a plant, containing nitrogen and usually oxygen) of curare was introduced in 1942 by Thomas Cullen. This purified alkaloid is called d-tubocurarine. Curare contains two alkaloids: curine, which paralyzes the muscle fibers of the heart, and curarine, which paralyzes the motor nerve endings in voluntary muscles.

That same year, a country doctor and part-time anesthetist named Harold Griffith of Montreal, Quebec, tested the use of curare in surgery. He used it as a muscle relaxant that let him use lower, safer doses of anesthesia. Over the next ten years, many doctors began using curare to relax their patients' muscles during abdominal surgery or during tracheal intubation (the inserting of a tube into the trachea to allow a patient to breathe).

Artificial Curare

Because the effects of natural curare were still unpredictable, Swiss-Italian pharmacologist Daniele Bovet (1907-1992; winner of the 1957 Nobel Prize in medicine) of the Pasteur Institute in Paris, France, set out to make a synthetic (artificially produced) uniform curare. He succeeded in 1947 with the medicine gallamine, and then went on to make more than 400 compounds that had the same effects as curare. One of these compounds, succinylcholine, became a widely used and effective curare substitute that could be given in precise dosages with predictable effects. Succinylcholine allows complete muscle relaxation during surgery without deep anesthesia.

While d-tubocurarine and similar compounds totally paralyze the muscles, they do not affect the central nervous system. A patient who receives an injection (shot) of this drug into a muscle quickly begins to feel dizzy and warm. The muscles of the jaw, neck, and head are the first to become weak and relaxed. The person can hear low tones better because small muscles in the middle ear relax. Then the arms and legs begin to feel heavy and difficult to move. Breathing becomes harder, and the patient experiences "shortness of breath," even with artificial respiration. He cannot swallow and feels like he is choking because saliva accumulates in the throat. Soon it is impossible to move at all. During this time the patient is fully conscious of everything around him and can sense pain. For this reason anesthesia is still needed during medical procedures, though in smaller amounts.

The effects of curare do not last long, and a person or animal who has been poisoned by this substance can fully recover if given artificial respiration until the poison wears off. The action of d-tubocurarine or its related compounds like succinylcholine begins to wear off after about 20 minutes if a single moderate dose is injected into a vein, the usual method of giving the drug. During surgery the patient may have to be given additional small doses of d-tubocurarine. The drug has little or no effect if taken by mouth, unless swallowed in very large doses.

Curare-like drugs are sometimes used to relax muscles when doctors are correcting dislocations or setting bone fractures, and in the control of muscle spasms during convulsions like those seen with tetanus, epilepsy, drug overdose, and following the bite of the black widow spider. These drugs are also used during tracheal intubation, and to help make examinations of the larynx, bronchial tubes, and esophagus easier.