CURARE

''

This page is about the plant toxins. For the DC Comics character, see Curare.''

'Curare' is a common name for various dart poisons (arrow poisons) originating from South America. The three main types, or families of curare are:

★ the tubocurare (also known as tube or bamboo curare, because of its packing into hollow bamboo tubes; main toxin is D-tubocurarine),

★ the calebas curare (also called "gourd curare" by older British classifications, being packed into hollow gourds; main toxins are alloferine and toxiferine)

★ and the pot curare (packed in terra cotta pots; main toxins are protocurarine, protocurine, and protocuridine).
Of these three families, some formulas belonging to the calebas curare are the most toxic, relative to their LD₅₀ values.

Contents

History

Pharmacological properties

Curare and anaesthesia

Plants from which primary components of curare can be extracted

Synonym

References

History

In 1596 Sir Walter Raleigh mentioned the arrow poison in his book ''Discovery of the Large, Rich, and Beautiful Empire of Guiana''. It is possible that the poison he described was not curare at all.^[1]
During 1811-1812 Sir Benjamin Collins Brody (1783-1862) experimented with curare ^[2] 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 (1783-1865) (who gained fame by riding a captured alligator) described a classical experiment in which he kept a curarized she-ass alive by artificial ventilation with a bellows through a tracheostomy.^[3] Waterton is also credited with bringing curare to Europe.^[4]
George Harley (1829-1896) showed in 1850 that curare (wourali) was effective for the treatment of tetanus and strychnine poisoning.^[5][6]
The most known and historically important (because of its medical applications) toxin is d-tubocurarine. It was isolated from the crude drug in 1935 by King (1887-1956) of London, working in Sir Henry Dale’s laboratory. He also established its chemical structure.^[7] It was introduced into anesthesiology in the early 1940s as a muscle relaxant for surgery. Curares are active (i.e. toxic or muscle relaxing, dependent on the intention of their use) only if given/applied parenterally, that is, by an injection, or direct wound contamination by poisoned dart/arrow tip. Curare compounds are too large and too highly charged to pass through the lining of the digestive tract. This is crucial, because the native tribes use curares mainly for hunting purposes, thus the curare-poisoned prey must remain safe to eat. In medicine, curare has been superseded by a number of curare-like agents (pancuronium, an alkaloid-like substance with steroidal skeleton in its molecule), that have a similar pharmacodynamic profile but with fewer side effects.
Curare has also been used historically as a paralyzing poison by South American indigenous people. The prey is killed by asphyxiation as the respiratory muscles are unable to contract resulting in apnea.

Pharmacological properties

Curare is an example of a non-depolarizing muscle relaxant (aka, competitive antagonist) which blocks the nicotinic receptors, one of the two types of cholinergic (acetylcholine) receptors on the post synaptic membrane of the neuromuscular junction. Curare does not occupy the agonist position, but likely binds within the channel pore.

Curare and anaesthesia

Isolated attempt to use curare during anesthesia dates back to 1912 by Arthur Lawen of Leipzig.^[8] But curare came to anesthesia via psychiatry (electroplexy). In 1939 Abram Elting and Bennett used it to modify metrazol induced convulsive therapy.^[9] 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 anaesthesia 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 [1].
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). 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. This has been completely disproved.^[10]Modern anaesthetists have at their disposal a variety of muscle relaxants for use as a standard component of anaesthesia.
The ability to produce muscle relaxation independently from anaesthesia has permitted anaesthesiologists to adjust the two effects separately as needed to ensure that their patients are safely unconscious and sufficiently relaxed to permit surgery. However, it has also made possible anaesthesia awareness, a condition in which, through error or accident, a patient remains fully conscious and sensitive to pain during surgery, but is unable to move and thus unable to alert attending staff to their state of awareness. This problem is greatly solved by BIS monitor

Plants from which primary components of curare can be extracted

★ ''Strychnos toxifera''

★ ''Chondrodendron tomentosum''

Synonym

Curare. Woorari. Woorara. Woorali. Wourali. Wouralia. Urari

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)
1. Carman J. A. ''Anaesthesia'' 1968, '23', 706.
2. ''Phil. Trans''. 1811, '101', 194; 1812, '102', 205.
3. Reprinted in "Classical File", ''Survey of Anesthesiology'' 1978, '22', 98.
4. http://www.yeoldelog.com/medicinal/curare.shtml
5. Paton A. ''Practitioner'' 1979, '223', 849
6. http://www.whonamedit.com/doctor.cfm/3230.html
7. King H. J. ''Chem. Soc''. 1935, '57', 1381; ''Nature, Lond''. 1935, '135', 469.
8. Lawen A. ''Beitr. klin. Chir''. 1912, '80', 168.
9. Bennett A. E. ''J. Am. Med. Ass''. 1940, '114', 322
10. Beecher H. K. and Todd D. P. ''Ann. Surg''. 1954, '140', 2 (reprinted in "Classical File", ''Survey of Anesthesiology'' 1971, '15' , 394, 496).