Batrachotoxin
Skeletal formula of batrachotoxin
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Stick model of batrachotoxin based on the crystal structure of batrachotoxinin A O-p-bromobenzoate[1]
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Ball-and-stick model of batrachotoxin, as above[1]
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Names | |
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Other names
3α,9α-epoxy-14β,18-(2′-oxyethyl-N-methylamino)-5β-pregna-7,16-diene-3β,11α,20α-triol 20α-2,4-dimethylpyrrole-3-carboxylate
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Identifiers | |
3D model (
JSmol ) |
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ChemSpider | |
IUPHAR/BPS |
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PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C31H42N2O6 | |
Molar mass | 538.685 g·mol−1 |
Density | 1.304 g/mL [2] |
Hazards | |
Occupational safety and health (OHS/OSH): | |
Main hazards
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Highly toxic |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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2 μg/kg (mouse, sub-cutaneous) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Batrachotoxin (BTX) is an extremely potent
History
Batrachotoxin was discovered by Fritz Märki and
Toxicity
According to experiments with rodents, batrachotoxin is one of the most potent alkaloids known: its intravenous LD50 in mice is 2–3 μg/kg.[8] Meanwhile, its derivative, batrachotoxinin A, has a much lower toxicity with an LD50 of 1000 μg/kg.[5]
The toxin is released through colourless or milky secretions from glands located on the back and behind the ears of frogs from the genus Phyllobates. When one of these frogs is agitated, feels threatened or is in pain, the toxin is reflexively released through several canals.
Batrachotoxin activity is temperature-dependent, with a maximum activity at 37 °C (99 °F). Its activity is also more rapid at an
Neurotoxicity
As a
This has a direct effect on the peripheral nervous system (PNS). Batrachotoxin in the PNS produces increased permeability (selective and irreversible) of the resting cell membrane to sodium ions, without changing potassium or calcium concentration. This influx of sodium depolarizes the formerly polarized cell membrane. Batrachotoxin also alters the ion selectivity of the ion channel by increasing the permeability of the channel toward larger cations. Voltage-sensitive sodium channels become persistently active at the resting membrane potential. Batrachotoxin kills by permanently blocking nerve signal transmission to the muscles.
Batrachotoxin binds to and irreversibly opens the sodium channels of nerve cells and prevents them from closing. The neuron can no longer send signals and this results in paralysis. Furthermore, the massive influx of sodium ions produces
Cardiotoxicity
Although generally classified as a
Treatment
This section needs additional citations for verification. (November 2022) |
Currently, no effective antidote exists for the treatment of batrachotoxin poisoning.[11] Veratridine, aconitine and grayanotoxin—like batrachotoxin—are lipid-soluble poisons which similarly alter the ion selectivity of the sodium channels, suggesting a common site of action. Due to these similarities, treatment for batrachotoxin poisoning might best be modeled after, or based on, treatments for one of these poisons. Treatment may also be modeled after that for digitalis, which produces somewhat similar cardiotoxic effects.
While it is not an antidote, the membrane depolarization can be prevented or reversed by either
Sources
Batrachotoxin has been found in four Papuan beetle species, all in the genus Choresine in the family Melyridae; C. pulchra, C. semiopaca, C. rugiceps and C. sp. A.[12][13]
Several species of bird endemic to
While the purpose for toxicity in these birds is not certain, the presence of batrachotoxins in these species is an example of convergent evolution. It is believed that these birds gain the toxin from batrachotoxin-containing insects that they eat and then secrete it through the skin.[13][17]
Batrachotoxin has also been found in all described species of the poison dart frog genus
The frogs do not produce batrachotoxin themselves. Just as in the birds, it is believed that these frogs gain the toxin from batrachotoxin-containing insects that they eat, and then secrete it through the skin.[13] Beetles in the genus Choresine are not found in Colombia, but it is thought that the frogs might get the toxin from beetles in other genera within the same family (Melyridae), several of which are found in Colombia.[12]
Frogs raised in captivity do not produce batrachotoxin, and thus may be handled without risk. However, this limits the amount of batrachotoxin available for research as 10,000 frogs yielded only 180 mg of batrachotoxin.[19] As these frogs are endangered, their harvest is unethical. Biosynthetic studies are also challenged by the slow rate of synthesis of batrachotoxin.[5]
The native habitat of poison dart frogs is the warm regions of Central and South America, in which the humidity is around 80 percent.
Use
The most common use of this toxin is by the Noanamá Chocó and Emberá Chocó of the Embera-Wounaan of western Colombia for poisoning blowgun darts for use in hunting.
Poison darts are prepared by the Chocó by first impaling a frog on a piece of wood.[20] By some accounts, the frog is then held over or roasted alive over a fire until it cries in pain. Bubbles of poison form as the frog's skin begins to blister. The dart tips are prepared by touching them to the toxin, or the toxin can be caught in a container and allowed to ferment. Poison darts made from either fresh or fermented batrachotoxin are enough to drop monkeys and birds in their tracks. Nerve paralysis is almost instantaneous. Other accounts say that a stick siurukida ("bamboo tooth") is put through the mouth of the frog and passed out through one of its hind legs. This causes the frog to perspire profusely on its back, which becomes covered with a white froth. The darts are dipped or rolled in the froth, preserving their lethal power for up to a year.
See also
- Tetrodotoxin, a toxin that works in the opposite way of batrachotoxin
Citations
- ^ S2CID 28609553.
- ^ Daly, J. W.; Journal of the American Chemical Society 1965, V87(1), P124-6 CAPLUS
- ^ The Merck Index. Entry 1009. p. 167.
- S2CID 19663576.
- ^ PMID 5814950.
- PMID 5689118.
- .
- PMID 5689118.
- S2CID 6343011.
- PMID 18690024.
- ^ a b "Poison Dart Frog - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2022-11-14.
- ^ PMID 15520388.
- ^ S2CID 205127015.
- ^ Avian chemical defense: Toxic birds not of a feather
- PMID 1439786.
- ^ Gill, F.; Donsker, D., eds. (2017). "Orioles, drongos & fantails". IOC World Bird List (v 7.2). Retrieved 10 June 2017.
- ^ "Academy Research: A Powerful Poison". California Academy of Science. Archived from the original on 2012-08-27. Retrieved 2013-05-10.
- S2CID 58605344.
- ^ Du Bois, Justin, et al., inventor; Board of Trustees of the Leland Stanford Junior University, assignee. Batrachotoxin Analogues, Compositions, Uses, and Preparation Thereof. US patent 2014/0171410 A1. June 19, 2014.
- ISBN 978-0226121987.
General and cited references
- Daly, J. W.; Witkop, B. (1971). "Chemistry and Pharmacology of Frog Venoms". In Bücherl, W.; Buckley, E. E.; Deulofeu, V. (eds.). Venomous Animals and Their Venoms. Vol. 2. New York: Academic Press. OCLC 299757.