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Curare

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.

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curare

curare is the name of a crude drug, existing in the form of a dark brown, sticky, plant extract, and characterized by containing considerable amounts of poisonous alkaloids. Curare was prepared by the South American Indian tribes living in the valleys of the Amazon and the Orinoco. The extracts were used as arrow poisons, for hunting, in a way which demonstrates a profound understanding of mechanisms. The flesh of animals killed by a poisoned arrow could be eaten with impunity, showing that the poison was lethal when injected, but not absorbed when taken orally. History does not tell us just how many attempts to develop arrow poisons had less fortunate outcomes. When Westerners turned their attention to the nature of South American arrow poisons there were considerable problems in discovering the active principles. Individual samples from the same region were often variable in composition. In some samples several hundred constituents could be detected, mainly of plant origin, but often including animal material, such as excreta, and sometimes soil. Attention eventually focussed on extracts of plants from the families Menispermaceae, particularly Chondrodendron species, and Loganiaceae. Curare became available in three major forms with different regional origins: packed into bamboo tubes (tube-curare); in gourds (calabash-curare) containing material from Strychnos species; and in earthenware pots (pot-curare). In 1935 Harold King, a chemist working for the Medical Research Council in London, extracted, from a sample of tube-curare from the British Museum, a crystalline alkaloid which he called tubocurarine. This was to have a major impact in medicine.

Tubocurarine blocks the effects of the neurotransmitter acetylcholine in sites where it acts on the type of post-synaptic membrane receptors which are known as nicotinic. Quite the most important sites of these receptors are the junctions between motor nerves and voluntary skeletal muscle. When injected — and this includes injection by poisoned arrow — control of voluntary muscles is lost and flight or escape is not possible. Long before King had investigated the structure of tubocurarine, Claude Bernard had shown in 1856 that curare blocked neuromuscular transmission, without affecting conduction in the nerve or the contractility of the muscle. We now know that curare competes with acetylcholine for combination with the receptors on the muscle membrane — causing neuromuscular block.

In surgery, access to body cavities is hampered by tension in the voluntary muscles. These can be relaxed using anaesthetics, but only if dangerous dosage levels are used. Another, rather awkward solution is for assistants to hold open the incision with retractor. Motor paralysis by tubocurarine offered a surer and less cumbersome alternative. Use of such muscle relaxants became widespread for major surgery from the mid twentieth century. Not all voluntary muscles are equally sensitive to tubocurarine, and fortunately the respiratory muscles are the most spared. Thus by careful control of the dosage respiration can be maintained, although it is usual for anaesthetists to control the ventilation of the lungs mechanically.

For many years the commercial supply of tubocurarine was by extraction from crude curare extracts. New synthetic drugs, such as atracurium, have now largely replaced tubocurarine in medical practice. Nevertheless, for a while, surgery owed a debt to the experimentation of primitive peoples with their need for an arrow poison.

Alan W. Cuthbert

Bibliography

Sneader, W. (1985). Drug discovery — the evolution of modern medicines. Wiley, Chichester.


See also acetylcholine; anaesthesia, general; neuromuscular junction; paralysis; membrane receptors.

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curare

curare (kyŏŏrär´ē), any of a variety of substances originally used as arrow poisons by Native South Americans in hunting and in warfare. The main active substance of curare, tubocurarine, is an alkaloid extracted from Chondodendron tomentosum, Strychnos toxifera, and other plant species. The poison produces muscle paralysis by interfering with the transmission of nerve impulses at the receptor sites of all skeletal muscle. Muscles with many nerves, such as eye muscles, are affected first. In recent years curare has been put to medical use. When given in small quantities with general anesthesia, especially in abdominal surgery, curare ensures the desired relaxation of muscle tissue with a minimal concentration of the anesthetic, lessening the possibilities of anesthesia-induced complications. Curare is also used to relieve spastic paralysis, to treat some mental disorders, and to induce muscle relaxation for the setting of fractures.

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curare

curare 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. Curare is used as an arrow poison by South American Indians and was formerly used as a muscle relaxant in surgery.

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curare

curare Poisonous resinous extract obtained from various tropical South American plants of the genera Chondodendron and Strychnos. Most of its active elements are alkaloids. Causing muscle paralysis, it is used on the poisoned arrows of Native South Americans when hunting. It is also used as a muscle relaxant in abdominal surgery and setting fractures.

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curare

cu·ra·re / k(y)oŏˈrärē/ • n. a bitter, resinous substance obtained from the bark and stems of certain South American plants (families Menispermaceae and Loganiaceae). It is traditionally used by some Indian peoples to poison their arrows and darts.

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curare

curare (kew-rar-i) n. an extract from the bark of South American trees (Strychnos and Chondodendron species) that relaxes and paralyses voluntary muscle. Curare was formerly employed to control the muscle spasms of tetanus and as a muscle relaxant in surgical operations.

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curare

curare A plant extract containing alkaloids that block the passage of nerve impulses at synaptic junctions by competing with acetylcholine for receptor sites on the post-synaptic membrane. It is used by some S. American Indians as an arrow poison. See also STRYCHNOS.

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curare

curare A plant extract containing alkaloids that block the passage of nerve impulses at synaptic junctions by competing with acetyl-choline for receptor sites on the post-synaptic membrane. It is used by some South American Indians as an arrow poison.

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curare

curare substance obtained from plants, used by S. Amer. Indians to poison arrows. XVIII.
Also woorara (XVIII), urari, (w)oorali, (wo)urali (all XIX). — Carib.

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curare

curareBarry, Carrie, carry, Cary, Clarrie, Gary, glengarry, harry, intermarry, Larry, marry, miscarry, parry, tarry •angry • chapelry • cavalry • lamprey •Crabtree •gantry, pantry •Langtry • polyandry •askari, Bari, Cagliari, calamari, Campari, charivari, curare, Ferrari, Harare, Kalahari, Mari, Mata Hari, Qatari, Rastafari, safari, sari, Scutari, shikari, sparry, starry, Stradivari, tamari, terramare, Vasari, Zanzibari •compadre • chantry •beriberi, berry, bury, Ceri, cherry, Derry, ferry, Gerry, jerry, Kerry, merry, perry, Pondicherry, sherry, terry, very, wherry •débris • Hendry • Geoffrey • belfry •devilry, revelry •Henri, henry •peltry •entry, gentry, sentry •pedantry •peasantry, pheasantry, pleasantry •vestry • every • elderberry •checkerberry • whortleberry •chokecherry • daredevilry •Londonderry • knobkerrie

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