Batrachotoxins are extremely potent cardiotoxic and neurotoxic steroidal alkaloids found in certain species of frogs (poison dart frog), Melyridae beetles and birds (Pitohui, Ifrita kowaldi). Cardiotoxicity is the occurrence of heart muscle damage. ... The term neurotoxic is used to describe a substance, condition or state that damages the nervous system and / or brain, usually by killing neurons. ... In chemistry and biology, Steroids are a type of lipid, characterized by a carbon skeleton with four fused rings. ... An alkaloid is a nitrogenous organic molecule that has a pharmacological effect on humans and other animals. ... Genera Many, about 150+ species within 9 genera Dendrobates auratus in Panama Colostethus flotator in Costa Rica Poison Dart Frog is the common name given to the group of frogs belonging to the family Dendrobatidae. ... Genus Pitohui Lesson, 1830 The Pitohuis are a genus of birds, endemic to New Guinea, belonging to the family Pachycephalidae. ...

Chemistry

The chemical structure of batrachotoxin

There are several types of batrachotoxins; batrachotoxin itself has the structure shown at right. drawn in bkchem (http://www. ...

Batrachotoxin comes from the Greek word "batrochos", meaning frog, and "toxin", meaning poison. It was named by scientists John Daly and Bernard Witkop, who isolated the pure alkaloid and determined its structure and chemical properties. Its chemical formula is C₃₁H₄₂N₂O₆.

More than 100 toxins have been identified from the skin secretions of members of the Dendrobatidae family of frogs, especially Dendrobates and Phyllobates. Members of the genus Dendrobates (of which there are at least 44 known species) are also known as "poison dart" or "poison arrow" frogs. However, only frogs of the genus Phyllobates produce the super-deadly batrachotoxin. Genera Many, about 150+ species within 8 genus Poison Dart Frog is the common name given to the group of Dendrobatid frogs belonging to the family of Dendrobatidae. ...

Toxicity

Batrachotoxin is one of the most potent venoms known. Extrapolating from the lethal dosage LD₅₀ in rats, the lethal dose of this alkaloid in humans is estimated to be 1 to 2 µg/kg. Thus, the lethal dose for a 68 kg (150 pound) person would be approximately 100 micrograms, or equivalent to the weight of two grains of ordinary (fine) table salt (NaCl). Batrachotoxin is more potent than curare (another arrow poison used by South American indians and derived from plants of the genera Strychnos and Curarea), and about ten times more potent than tetrodotoxin, from the puffer fish. An LD50 test being administered In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. ... Strychnos toxifera by Koehler 1887 Curare is a substance containing the alkaloid D-tubocurarine. ... Species about 190 Strychnos is a genus of flowering plants, belonging to family Loganiaceae. ... Tetrodotoxin (anhydrotetrodotoxin 4-epitetrodotoxin, tetrodonic acid, TTX) is a potent neurotoxin, which blocks action potentials in nerves by binding to the pores of voltage-gated sodium channels in nerve cell membranes. ... Genera Amblyrhynchotes Arothron Auriglobus Canthigaster Carinotetraodon Chelonodon Colomesus Contusus Ephippion Feroxodon Fugu Gastrophysus Javichthys Lagocephalus Liosaccus Marilyna Monotretus Omegaphora Pelagocephalus Polyspina Reicheltia Sphoeroides Takifugu Tetractenos Tetraodon Torquigener Tylerius Xenopterus The pufferfish, also called blowfish, swellfish, balloonfish are fish making up the family Tetraodontidae, within the order Tetraodontiformes. ...

The toxin is released through colorless 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.

It is a neurotoxin which affects the nervous system. All the diverse pharmacological effects result from depolarization of nerve and muscle fibres due to increased sodium ion permeability of the excitable cell membrane. Lipid-soluble toxins such as batrachotoxin act directly on sodium channels involved in action potential generation and by modifying both their ion selectivity and voltage sensitivity. A neurotoxin is a toxin that acts specifically on nerve cells – neurons – usually by interacting with membrane proteins and ion channels. ...

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. Permeability has several meanings: In electromagnetism, permeability is the degree of magnetisation of a material in response to a magnetic field. ...

Although generally classified as a neurotoxin, batrachotoxin has marked effects on heart muscles. These effects are similar to the cardiotoxic effects of digitalis (digoxin), a poison found in the foxglove plant. Batrachotoxin interferes with heart conduction, causing arrhythmias, extra systoles, ventricular fibrillation and other changes which lead to cardiac arrest. Batrachotoxin induces a massive release of acetylcholine in nerves and muscles and destruction of synaptic vesicles, as well. Batrachotoxin R is more effective than related batrachotoxin A. A neurotoxin is a toxin that acts specifically on nerve cells – neurons – usually by interacting with membrane proteins and ion channels. ... Digoxin is a cardiac glycoside extracted from the foxglove plant, digitalis. ... Species Digitalis ferruginea Digitalis grandiflora Digitalis lanata Digitalis lutea Digitalis obscura Digitalis purpurea Digitalis is a genus of about 20 species of herbaceous biennials, perennials and shrubs in the foxglove family Scrophulariaceae. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... In a neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various neurotransmitters that are released during calcium-regulated exocytosis at the presynaptic terminal into the synaptic cleft of a synapse. ...

Structural changes in nerves and muscles are due to a massive influx of sodium ions, which produces osmotic alterations. It has been suggested that there may also be an effect on the central nervous system, although it is not currently known what such an effect may be.

Batrachotoxin activity is temperature-dependent, with a maximum activity at 37 degrees Celsius. Its activity is also more rapid at an alkaline pH, which suggests that the unprotonated form may be more active. The common (Arrhenius) definition of a base is a chemical compound that either donates hydroxide ions or absorbs hydrogen ions when dissolved in water. ...

Treatment

Currently no effective antidote exists for the treatment of batrachotoxin poisoning. 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. Categories: Biochemistry stubs | Neurotoxins ... Grayanotoxin is a toxin found in rhododendrons and other plants of the family Ericaceae. ... Species About 20 species, including: Digitalis ciliata Digitalis davisiana Digitalis dubia Digitalis ferruginea Digitalis grandiflora Digitalis laevigata Digitalis lanata Digitalis lutea Digitalis obscura Digitalis parviflora Digitalis purpurea Digitalis thapsi Digitalis viridiflora Digitalis is a genus of about 20 species of herbaceous biennials, perennials and shrubs that was traditionally placed in...

While it is not an antidote, the membrane depolarization can be prevented or reversed by either tetrodotoxin (from puffer fish), which is a noncompetitive inhibitor, or saxitoxin ("red tide"). These both have effects antagonistic to those of batrachotoxin on sodium flux. Certain anesthetics may act as antagonists to the action of this alkaloid poison, while other local anesthetics block its action altogether by acting as competitive antagonists. Tetrodotoxin (anhydrotetrodotoxin 4-epitetrodotoxin, tetrodonic acid, TTX) is a potent neurotoxin, which blocks action potentials in nerves by binding to the pores of voltage-gated sodium channels in nerve cell membranes. ... Saxitoxin (STX), is a neurotoxin found in marine dinoflagellates. ...

Source

The "poison dart" (or "poison arrow") frog does not produce batrachotoxin itself. Over the span of millions of years, subtle modifications of the frog's receptors have made it insensitive to the effects of the toxin. It is believed that the frogs get the poison from eating ants or other insects in their native habitat, and the insects obtain the poison from a plant source. Frogs raised in captivity do not produce batrachotoxin, and thus may be handled without the risk of death.

The native habitat of poison dart frogs is the warm regions of Central America and South America in which the humidity is around 80 percent.

Of the three so-called "poison dart" frogs which contain batrachotoxin - Phyllobates terribilis, Phyllobates aurotaenia, and Phyllobates bicolor - the most toxic is the most recently discovered Phyllobates terribilis.

Phyllobates terribilis produces 27 times more batrachotoxin than its close relatives and is 20-fold more toxic. One freshly caught frog has up to 2 milligrams of toxin. Just a small fraction of that would be lethal if it reached an open wound on human skin. One frog has enough batrachotoxin to poison 50 darts and kill 50 men.

Use

The most common use of this toxin is by the Noanamá Chocó and Emberá Chocó Indians of western Colombia for poisoning blowgun darts for use in hunting.

Poison darts are prepared by the Chocó Indians by first impaling a frog on a piece of wood. 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 its destructive power for up to a year.