Dictionary:
cu·ra·re cu·ra·ri (kʊ-rä'rē, kyʊ-)  |
[Portuguese or Spanish curaré, both of Cariban and Tupian origin.]
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| Chemistry Dictionary: 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.
| Britannica Concise Encyclopedia: curare |
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| World of the Body: 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
See also acetylcholine; anaesthesia, general; neuromuscular junction; paralysis; membrane receptors.
| Columbia Encyclopedia: curare |
| Veterinary Dictionary: curare |
Any of a wide variety of highly toxic extracts from various botanical sources, including species of Strychnos, a genus of tropical trees; used originally as arrow poisons in South America. A form extracted from the shrub, Chondrodendron tomentosum, has been used as skeletal muscle relaxant. The active principle is d-tubocurarine.
| Wikipedia: Curare |
Curare IPA: [k(j)uːˈrɑːri] [1] is a common name for various arrow poisons originating from South America. The three main types of curare are:
Of these three types, some formulas belonging to the calebas curare are the most toxic, relative to their LD50 values.
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Curare has been used historically as a paralyzing poison by South American indigenous people. The prey is killed by arrows or blowgun darts that are dipped in curare, which leads to asphyxiation as the respiratory muscles of the hunted animal are unable to contract. The word curare is derived from woorari, a native South American word meaning poison.
In 1596 Sir Walter Raleigh mentioned the arrow poison in his book Discovery of the Large, Rich, and Beautiful Empire of Guiana (now Guyana), though it is possible that the poison he described was not curare at all.[2] In 1780, Abbe Felix Fontana discovered that it acted on the capability of voluntary muscles rather than on nerves and the heart.[3] In 1800, Alexander von Humboldt gave the first western account of how the toxin was prepared from plants by Orinoco River natives.[4]
During 1811-1812 Sir Benjamin Collins Brody (1783-1862) experimented with curare.[5] He was the first to show that curare does not kill the animal and the recovery is complete if the animal’s respiration is maintained artificially. In 1825 Charles Waterton described a classical experiment in which he kept a curarized female donkey alive by artificial respiration with a bellows through a tracheostomy.[6] Waterton is also credited with bringing curare to Europe.[7] Robert Hermann Schomburgk, who was a trained botanist, identified the vine as one of the Strychnos genus and gave it the now accepted name Strychnos toxifera.[8]
George Harley (1829-1896) showed in 1850 that curare (wourali) was effective for the treatment of tetanus and strychnine poisoning.[9][10] From 1887 the Burroughs Wellcome catalogue listed under its 'Tabloids' brand name, tablets of curare at 1/12 grain (price 8 shillings) for use in preparing a solution for hypodermic injection. In 1914 Henry Hallett Dale (1875-1968) described the physiological actions of acetylcholine.[11] After twenty-five years he showed that acetylcholine is responsible for neuromuscular transmission which can be blocked by curare.[12]
The best known and historically most important toxin (because of its medical applications) is d-tubocurarine. It was isolated from the crude drug (from a museum sample of curare) in 1935 by Harold King (1887-1956) of London, working in Sir Henry Dale’s laboratory. He also established its chemical structure.[13] It was introduced into anesthesia in the early 1940s as a muscle relaxant for surgery. Curares are active — toxic or muscle-relaxing, depending on the intention of their use — only by an injection or a direct wound contamination by poisoned dart or arrow. It is harmless if taken orally[6][14] because curare compounds are too large and too highly charged to pass through the lining of the digestive tract to be absorbed into the blood. For this reason, native tribes are able to safely eat curare-poisoned prey. In medicine, curare has been superseded by a number of curare-like agents, such as pancuronium, which have a similar pharmacodynamic profile but fewer side effects.
Curare is an example of a non-depolarizing muscle relaxant that blocks the nicotinic acetylcholine receptor (nAChR), one of the two types of acetylcholine (ACh) receptors. The main toxin of curare, d-tubocurarine, occupies the same position on the receptor as ACh with an equal or greater affinity, and elicits no response, making it a competitive antagonist. The antidote for curare poisoning is an acetylcholinesterase (AChE) inhibitor (anti-cholinesterase), such as physostigmine or neostigmine. By blocking ACh degradation, AChE inhibitors raise the amount of ACh in the neuromuscular junction; the accumulated ACh will then correct for the effect of the curare by activating the receptors not blocked by toxin at a higher rate.
Isolated attempts to use curare during anesthesia date back to 1912 by Arthur Lawen of Leipzig.[15] But curare came to anesthesia via psychiatry (electroplexy). In 1939 Abram Elting Bennett used it to modify metrazol induced convulsive therapy.[16] Muscle relaxants are used in modern anesthesia for many reasons, such as providing optimal operating conditions and facilitating intubation of the trachea. Before muscle relaxants, anesthesiologists needed to use larger doses of the anesthetic agent, such as ether, chloroform or cyclopropane to achieve these aims. Such deep anesthesia risked killing patients that were elderly or had heart conditions. The source of curare in the Amazon was first researched by Richard Evans Schultes in 1941. Since the 1930s, it was being used in hospitals as a muscle relaxant. He discovered that different types of curare called for as many as 15 ingredients, and in time helped to identify more than 70 species that produced the drug.
On January 23, 1942, Dr. Harold Griffith and Dr. Enid Johnson gave a synthetic preparation of curare (Intracostin/ Intocostrin) to a patient undergoing an appendectomy (to supplement conventional anesthesia). Curare (d-tubocurarine) is no longer used for anesthesia during surgery as better drugs are now available. When used with halothane d-tubocurarine can cause profound fall in blood pressure in some patients as both the drugs are ganglion blockers.[17] However, it is safer to use d-tubocurarine with ether.
In 1954, a sensational article was published by Beecher and Todd suggesting that the use of muscle relaxants (drugs similar to curare) increased death due to anesthesia nearly six fold.[18] This has been completely disproved.
Modern anesthetists have at their disposal a variety of muscle relaxants for use in anesthesia. The ability to produce muscle relaxation independently from anesthesia has permitted anesthesiologists to adjust the two effects separately as needed to ensure that their patients are safely unconscious and sufficiently relaxed to permit surgery. The use of neuromuscular blocking drugs carries with it a very small risk of anaesthesia awareness.
Curare is also known as Ampi, Woorari, Woorara, Woorali, Wourali, Wouralia, Ourare, Ourari, Urare, Urari, and Uirary.
d-Tubocurarine, the popular alkaloid of Curare used as a medicine, was available as Tubocurarin, Tubocurarinum, Delacurarine, Tubarine, Metubine, Jexin, HSDB 2152, Isoquinoline Alkaloid, Tubadil, Mecostrin, Intracostin and Intocostrin.
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 | Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved. Read more |
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| Chemistry Dictionary. A Dictionary of Chemistry. Sixth Edition. Copyright © Market House Books Ltd, 2008. All rights reserved. Read more |
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| Britannica Concise Encyclopedia. Britannica Concise Encyclopedia. © 2006 Encyclopædia Britannica, Inc. All rights reserved. Read more |
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| World of the Body. The Oxford Companion to the Body. Copyright © 2001, 2003 by Oxford University Press. All rights reserved. Read more |
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| Columbia Encyclopedia. The Columbia Electronic Encyclopedia, Sixth Edition Copyright © 2003, Columbia University Press. Licensed from Columbia University Press. All rights reserved. www.cc.columbia.edu/cu/cup/. Read more |
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| Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved. Read more |
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