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クラーレ(南米原住民が矢じりに塗る植物から採った毒)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/27 22:52:40」(JST)

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This article is about the plant toxins. For the DC Comics character, see Curaré (Batman Beyond).

Not to be confused with Curara.

Strychnos toxifera by Koehler 1887

Curare /kjuːˈrɑːriː/^[1] is a common name for various arrow poisons originating from South America. The three main types of curare are:

tubocurare (also known as tube or bamboo curare, because of its packing into hollow bamboo tubes; main toxin is D-tubocurarine). It is a mono-quaternary alkaloid, an isoquinoline derivative.
calebas curare (also called "gourd curare" by older British classifications, being packed into hollow gourds; main toxins are alloferine and toxiferine)
pot curare (packed in terra cotta pots; main toxins are protocurarine, protocurine, and protocuridine).

Of these three types, some formulas belonging to the calebas curare are the most toxic, relative to their LD₅₀ values.

History

Curare was used as a paralyzing poison by South American indigenous people. The prey was shot by arrows or blowgun darts dipped in curare, leading to asphyxiation owing to the inability of the victim's respiratory muscles to contract. The word curare is derived from wurari, from the Carib language of the Macusi Indians of Guyana.^[2]

In 1596 Sir Walter Raleigh mentioned the arrow poison in his book Discovery of the Large, Rich, and Beautiful Empire of Guiana (which relates to his travels in Trinidad and Guayana), though it is possible that the poison he described was not curare.^[3] In 1780, Abbe Felix Fontana discovered that it acted on the voluntary muscles rather than the nerves and the heart.^[4] In 1800, Alexander von Humboldt gave the first western account of how the toxin was prepared from plants by Orinoco River natives.^[5]

During 1811-1812 Sir Benjamin Collins Brody (1783–1862) experimented with curare.^[6] 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.^[7] Waterton is also credited with bringing curare to Europe.^[8] 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.^[9]

George Harley (1829–1896) showed in 1850 that curare (wourali) was effective for the treatment of tetanus and strychnine poisoning.^[10]^[11] 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.^[12] After twenty-five years he showed that acetylcholine is responsible for neuromuscular transmission, which can be blocked by curare.^[13]

The best known and historically most important (because of its medical applications) toxin 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.^[14] It was introduced into anesthesia in the early 1940s as a muscle relaxant for surgery. Curare is active — toxic or muscle-relaxing, depending on the intended use — only by an injection or a direct wound contamination by poisoned dart or arrow. It is harmless if taken orally^[7]^[15] because curare compounds are too large and 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 eat curare-poisoned prey safely. 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.

Pharmacological properties

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, at the neuromuscular junction. 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.

The time of onset varies from within one minute (for tubocurarine in intravenous administration, penetrating a larger vein), to between 15 and 25 minutes (for intramuscular administration, where the substance is applied in muscle tissue).^[16]

Curare has no effect if ingested so the meat of an animal killed by curare does not become poisonous, and it has no effect on its flavor.^[17]

Anesthesia

Isolated attempts to use curare during anesthesia date back to 1912 by Arthur Lawen of Leipzig,^[18] but curare came to anesthesia via psychiatry (electroplexy). In 1939 Abram Elting Bennett used it to modify metrazol induced convulsive therapy.^[19] 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.

In the 1940s it was used on a few occasions during surgery as it was mistakenly thought to be an analgesic or anesthetic. The patients reported feeling the full intensity of the pain though they were not able to do anything about it since they were essentially paralyzed.^[20]

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). Safer curare derivatives, such as rocuronium and pancuronium, have superseded d-tubocurarine 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.^[21] 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.^[22] This has been completely disproven.^{[citation needed]}

Modern anesthetists have at their disposal a variety of muscle relaxants for use in anesthesia. The ability to produce muscle relaxation independently from sedation has permitted anesthetists 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 anesthesia awareness.

Plants from which primary components of curare can be extracted

Strychnos toxifera
Chondrodendron tomentosum

Diagnosis of curare poisoning

Curare poisoning can be indicated by typical signs of neuromuscular-blocking drugs such as paralysis including respiration but not directly affecting the heart.

Traditionally prepared curare is a dark, heavy, viscid paste with a very bitter taste.^[23]

Management of curare poisoning

Curare poisoning can be managed by artificial respiration such as mouth-to-mouth resuscitation. In a study of 27 army volunteers that were paralyzed with curare, artificial respiration managed to keep an oxygen saturation of always above 85%,^[24] a level at which there is no evidence of altered state of consciousness.^[25] Yet, curare poisoning mimics the total locked-in syndrome in that there is paralysis of every voluntarily controlled muscle in the body (including the eyes), making it practically impossible for the victim to confirm consciousness while paralyzed.^[26]

Spontaneous breathing is resumed after the end of the duration of action of curare, which is generally between 30 minutes^[27] to 8 hours,^[28] depending on the variant of the toxin and dosage. If available, the muscle paralysis can be reversed by administration of a cholinesterase inhibitor such as physostigmine.^[29]

Cardiac muscle is not affected by curare, generally making cardiac resuscitation such as chest compressions unnecessary.

Names

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.

Wikisource has original text related to this article:

Curare

Notes

^ "curare". Oxford English Dictionary (3rd ed.). Oxford University Press. 2001. http://oed.com/search?searchType=dictionary&q=curare.
^ http://www.etymonline.com/index.php?term=curare
^ Carman J. A. Anaesthesia 1968, 23, 706.
^ The Gale Encyclopedia of Science. Third Edition.
^ [1]Personal Narrative of Travels to the Equinoctial Regions of America, During the Year 1799-1804 — Volume 2, Humboldt, Alexander von
^ Phil. Trans. 1811, 101, 194; 1812, 102, 205.
^ ^a ^b Arrow Poison to Surgical Muscle Relaxant
^ Reprinted in "Classical File", Survey of Anesthesiology 1978, 22, 98.
^ Waterton and Wouralia. British Journal of Pharmacology (1999) 126, 1685–1689
^ Paton A. Practitioner 1979, 223, 849
^ George Harley
^ Dale H. H. J. Pharmac. Exp. Ther. 1914, 6, 147.
^ Dale H. H. Br. Med. J. 1934, 1, 835
^ King H. J. Chem. Soc. 1935, 57, 1381; Nature, Lond. 1935, 135, 469.
^ Curare - Chondrodendron tomentosum
^ Curare in Drugs.com. Revised: 11/08/2001
^ From the Rainforests of South America to The Operating Room: A History of Curare, By Daniel Milner, BA, CD, Summer 2009. University of Ottawa Faculty of Medicine.
^ Lawen A. Beitr. klin. Chir. 1912, 80, 168.
^ Bennett A. E. J. Am. Med. Ass. 1940, 114, 322
^ Dennett, Daniel C. Brainstorms: Philosophical Essays on Mind and Psychology (1978), Cambridge, MA : MIT Press, p209
^ Mashraqui S. Hypotension induced with d-tubocurarine and halothane for surgery of patent ductus arteriosus. Indian Journal of Anesthesia. 1994 Oct; 42(5): 346-50
^ Beecher H. K. and Todd D. P. (1954). "A Study of the Deaths Associated with Anesthesia and Surgery : Based on a Study of 599,548 Anesthesias in Ten Institutions 1948-1952, Inclusive". Ann. Surg (reprinted in "Classical File", Survey of Anesthesiology 1971, 15 , 394, 496) 140 (2): 2–35. PMC 1609600. PMID 13159140. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1609600/.
^ Curare, a South American Arrow Poison, from "Plants and Civilization" by Professor Arthur C. Gibson, at UCLA Mildred E. Mathias Botanical Garden.
^ Page 520 in: Paradis, Norman A. (2007). Cardiac arrest: the science and practice of resuscitation medicine. Cambridge, UK: Cambridge University Press. ISBN 0-521-84700-1.
^ Oxymoron: Our Love-Hate Relationship with Oxygen, By Mike McEvoy at Albany Medical College, New York. 10/12/2010
^ Page 357 in: Damasio, Antonio R. (1999). The feeling of what happens: body and emotion in the making of consciousness. San Diego: Harcourt Brace. ISBN 0-15-601075-5.
^ For therapeutic dose of tubocurarine by shorter limit as given at page 151 in: Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. OCLC 51622037.
^ For 20-fold paralytic dose of toxiferine ("calebas curare"), according to: Page 330 in: The Alkaloids: v. 1: A Review of Chemical Literature (Specialist Periodical Reports). Cambridge, Eng: Royal Society of Chemistry. 1971. ISBN 0-85186-257-8.
^ Page 153 in: Thomas Morgan III; Bernadette Kalman (2007). Neuroimmunology in Clinical Practice. Wiley-Blackwell. ISBN 1-4051-5840-9.

References

Foldes, F.F. "Anesthesia before and after curare", Anasthesieabteilung des Albert-Einstein-College of Medicine. Anaesthesiol Reanim, 1993, 18(5):128-31. (retrieved June 20, 2005)
James, Mel. "Harold Griffith",Heirloom Series, Volume 6. (retrieved June 20, 2005)
"Curare", Blue Planet Biomes, 2000. (retrieved September 27, 2005)
Smith, Roger. "Cholernergic Transmission", (retrieved March 13, 2007)
Strecker G J et al. "Curare binding and the curare-induced subconductance state of the acetylcholine receptor channel.", Biophysical Journal 56: 795-806 (1989). (retrieved May 12, 2007)

External links

Charles Waterton's book Wanderings in South America Free version
Neuromuscular blocking drugs: discovery and development

UpToDate Contents

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1. 神経筋接合部の電気診断学的評価 electrodiagnostic evaluation of the neuromuscular junction
2. 新規発症の蕁麻疹 new onset urticaria
3. ボツリヌス中毒 botulism
4. 換気調節 control of ventilation
5. 重症疾患に関連する神経筋脱力 neuromuscular weakness related to critical illness

English Journal

Alpha neurotoxins.

Barber CM, Isbister GK, Hodgson WC.SourceMonash Venom Group, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
Toxicon : official journal of the International Society on Toxinology.Toxicon.2013 Feb 13. pii: S0041-0101(13)00053-6. doi: 10.1016/j.toxicon.2013.01.019. [Epub ahead of print]
α-Neurotoxins have been isolated from hydrophid, elapid and, more recently, colubrid snake venoms. Also referred to as postsynaptic neurotoxins or 'curare' mimetic neurotoxins, they play an important role in the capture and/or killing of prey by binding to the nicotinic acetylcholine receptor on th
PMID 23416229

[Curares and timbós, poisons used in the Amazon].

Carod-Artal FJ.SourceFacultad de Medicina y Ciencias de la Salud, Universitat Internacional de Catalunya, Barcelona, España. fjcarod-artal@hotmail.com
Revista de neurologia.Rev Neurol.2012 Dec 1;55(11):689-98.
INTRODUCTION: The natives that dwell along the banks of the Orinoco and Amazon rivers have used different poisons from plants for centuries. The study reviews the historical and ethnographic aspects of the use of curares and timbós in the Amazonian region.DEVELOPMENT: Curare is prepared by boiling
PMID 23172095

Japanese Journal

Studies on sea snake venom

TAMIYA Nobuo,YAGI Tatsuhiko
Proceedings of the Japan Academy. Series B 87(3), 41-52, 2011
… The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor on the post synaptic membrane in a manner similar to that of curare. …
NAID 130000669109

クラーレとクロード・ベルナール : 日本の学界はどう受け入れたか?

竹中祐典
薬史学雑誌 41(1), 18-26, 2006-06-30
NAID 10025721404

Related Pictures

★リンクテーブル★

リンク元	「神経筋接合部」「クラーレ」

「神経筋接合部」

　　[★]

英: neuromuscular junction (K)
同: 神経筋シナプス neuromuscular synapse

神経筋接合部は軸索終末，シナプス間隙，筋細胞膜から構成される。