Curare 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 values.
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. In 1780, Abbe Felix Fontana discovered that it acted on the capability of voluntary muscles rather than on nerves and the heart. In 1800, Alexander von Humboldt gave the first western account of how the toxin was prepared from plants by Orinoco River natives.
During 1811-1812 Sir Benjamin Collins Brody (1783–1862) experimented with curare. 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. Waterton is also credited with bringing curare to Europe. 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.
George Harley (1829–1896) showed in 1850 that curare (wourali) was effective for the treatment of tetanus and strychnine poisoning. 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. After twenty-five years he showed that acetylcholine is responsible for neuromuscular transmission which can be blocked by curare.
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. 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 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 rocuronium, which have a similar pharmacodynamic profile but fewer side effects.
On January 23, 1942, Dr. Harold Griffith and Dr. Enid Johnson gave a synthetic preparation of curare (Intercostrin/ 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 a profound fall in blood pressure in some patients as both the drugs are ganglion blockers. 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 sixfold. This has been completely disproved.
Modern anaesthetists have at their disposal a variety of muscle relaxants for use in anaesthesia. The ability to produce muscle relaxation independently from sedation has permitted anaesthetists 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.
d-Tubocurarine, the popular alkaloid of Curare used as a medicine.
Category:Muscle relaxants Category:Nicotinic antagonists Category:Neurotoxins
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