Names | |
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IUPAC name (5S)-5-[(Dimethylamino)methyl]-1-{[hydroxy(methoxy)phosphoryl]oxy}-4,5-dihydro-1H-imidazol-2-amine | |
Identifiers | |
3D model (JSmol) | |
ChemSpider | |
KEGG | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C7H17N4O4P | |
Molar mass | 252.211 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Guanitoxin (GNT), formerly known as anatoxin-a(S) "Salivary" [a] , [1] is a naturally occurring cyanotoxin commonly isolated from cyanobacteria (specifically of the genus Anabaena). It is a potent covalent acetylcholinesterase inhibitor, and thus a potent rapid acting neurotoxin which in cases of severe exposure can lead to death. Guanitoxin was first structurally characterized in 1989, and consists of a cyclic N-hydroxyguanidine organophosphate with a phosphate ester moiety. [2]
The main mechanism of action for guanitoxin is by irreversibly inhibiting the active site of acetylcholinesterase leading to excess acetylcholine in the parasympathetic and peripheral nervous systems; inducing poisoning via nicotinic and muscarinic cholinergic receptor stimulation. [3] The clinical signs of high level guanitoxin exposure consists mainly of excessive salivation, lacrimation, chromodacryorrhea (in rats), urinary incontinence, muscular weakness, muscle twitching, convulsion, including opisthotonus, and respiratory distress and/or failure, and death. [4] [5]
Treatment of afflicted case by atropine has attested to suppress the muscarinic mediated toxicity; which prevents the namesake salivation that similarly reacts to prevent the toxin's other poisoning symptoms which include lacrimation, urinary incontinence and defecation. Atropine will not, however, counter another mechanism of the compounds toxicity as it also mediates a nicotinic adverse toxicity affecting muscle tremors, fasciculation, convulsions and respiratory failure.[ citation needed ]
Guanitoxin is generally labile. It decomposes rapidly in basic solutions, but is relatively stable in neutral or acidic solutions (pH 3-5). When stored at -20˚C, it slowly undergoes hydrolysis giving pre-guanitoxin N-oxide and monomethyl-phosphate, and more slowly, formation of pre-guanitoxin. Furthermore, air evaporation of guanitoxin solutions resulted in significant hydrolysis to pre-guanitoxin N-oxide. [2]
Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter. Nerve agents are irreversible acetylcholinesterase inhibitors used as poison.
Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.
Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested. Muscarine has been found in harmless trace amounts in Boletus, Hygrocybe, Lactarius and Russula. Trace concentrations of muscarine are also found in Amanita muscaria, though the pharmacologically more relevant compound from this mushroom is the Z-drug-like alkaloid muscimol. A. muscaria fruitbodies contain a variable dose of muscarine, usually around 0.0003% fresh weight. This is very low and toxicity symptoms occur very rarely. Inocybe and Clitocybe contain muscarine concentrations up to 1.6%.
Neurotoxins are toxins that are destructive to nerve tissue. Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol, glutamate, nitric oxide, botulinum toxin, tetanus toxin, and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations.
Microcystins—or cyanoginosins—are a class of toxins produced by certain freshwater cyanobacteria, commonly known as blue-green algae. Over 250 different microcystins have been discovered so far, of which microcystin-LR is the most common. Chemically they are cyclic heptapeptides produced through nonribosomal peptide synthases.
Chlorfenvinphos is an organophosphorus compound that was widely used as an insecticide and an acaricide. The molecule itself can be described as an enol ester derived from dichloroacetophenone and diethylphosphonic acid. Chlorfenvinphos has been included in many products since its first use in 1963. However, because of its toxic effect as a cholinesterase inhibitor it has been banned in several countries, including the United States and the European Union. Its use in the United States was discontinued in 1991.
Cyanotoxins are toxins produced by cyanobacteria. Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such concentrations that they can poison and even kill animals and humans. Cyanotoxins can also accumulate in other animals such as fish and shellfish, and cause poisonings such as shellfish poisoning.
Paralytic shellfish poisoning (PSP) is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks. These shellfish are filter feeders and accumulate neurotoxins, chiefly saxitoxin, produced by microscopic algae, such as dinoflagellates, diatoms, and cyanobacteria. Dinoflagellates of the genus Alexandrium are the most numerous and widespread saxitoxin producers and are responsible for PSP blooms in subarctic, temperate, and tropical locations. The majority of toxic blooms have been caused by the morphospecies Alexandrium catenella, Alexandrium tamarense, Gonyaulax catenella and Alexandrium fundyense, which together comprise the A. tamarense species complex. In Asia, PSP is mostly associated with the occurrence of the species Pyrodinium bahamense.
A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine.
Pralidoxime or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to treat organophosphate poisoning in conjunction with atropine and either diazepam or midazolam. It is a white solid.
Phosmet is a phthalimide-derived, non-systemic, organophosphate insecticide used on plants and animals. It is mainly used on apple trees for control of codling moth, though it is also used on a wide range of fruit crops, ornamentals, and vines for the control of aphids, suckers, mites, and fruit flies.
Anabaena circinalis is a species of Gram-negative, photosynthetic cyanobacteria common to freshwater environments throughout the world. Much of the scientific interest in A. circinalis owes to its production of several potentially harmful cyanotoxins, ranging in potency from irritating to lethal. Under favorable conditions for growth, A. circinalis forms large algae-like blooms, potentially harming the flora and fauna of an area.
Anatoxin-a, also known as Very Fast Death Factor (VFDF), is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity. It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin is produced by multiple genera of cyanobacteria and has been reported in North America, South America, Central America, Europe, Africa, Asia, and Oceania. Symptoms of anatoxin-a toxicity include loss of coordination, muscular fasciculations, convulsions and death by respiratory paralysis. Its mode of action is through the nicotinic acetylcholine receptor (nAchR) where it mimics the binding of the receptor's natural ligand, acetylcholine. As such, anatoxin-a has been used for medicinal purposes to investigate diseases characterized by low acetylcholine levels. Due to its high toxicity and potential presence in drinking water, anatoxin-a poses a threat to animals, including humans. While methods for detection and water treatment exist, scientists have called for more research to improve reliability and efficacy. Anatoxin-a is not to be confused with guanitoxin, another potent cyanotoxin that has a similar mechanism of action to that of anatoxin-a and is produced by many of the same cyanobacteria genera, but is structurally unrelated.
Cylindrospermopsin is a cyanotoxin produced by a variety of freshwater cyanobacteria. CYN is a polycyclic uracil derivative containing guanidino and sulfate groups. It is also zwitterionic, making it highly water soluble. CYN is toxic to liver and kidney tissue and is thought to inhibit protein synthesis and to covalently modify DNA and/or RNA. It is not known whether cylindrospermopsin is a carcinogen, but it appears to have no tumour initiating activity in mice.
Organophosphate poisoning is poisoning due to organophosphates (OPs). Organophosphates are used as insecticides, medications, and nerve agents. Symptoms include increased saliva and tear production, diarrhea, vomiting, small pupils, sweating, muscle tremors, and confusion. While onset of symptoms is often within minutes to hours, some symptoms can take weeks to appear. Symptoms can last for days to weeks.
Aphanizomenon is a genus of cyanobacteria that inhabits freshwater lakes and can cause dense blooms. They are unicellular organisms that consolidate into linear (non-branching) chains called trichomes. Parallel trichomes can then further unite into aggregates called rafts. Cyanobacteria such as Aphanizomenon are known for using photosynthesis to create energy and therefore use sunlight as their energy source. Aphanizomenon bacteria also play a big role in the Nitrogen cycle since they can perform nitrogen fixation. Studies on the species Aphanizomenon flos-aquae have shown that it can regulate buoyancy through light-induced changes in turgor pressure. It is also able to move by means of gliding, though the specific mechanism by which this is possible is not yet known.
Chlorethoxyfos is an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is registered for the control of corn rootworms, wireworms, cutworms, seed corn maggot, white grubs and symphylans on corn. The insecticide is sold under the trade name Fortress by E.I. du Pont de Nemours & Company.
Ethoprophos (or ethoprop) is an organophosphate ester with the formula C8H19O2PS2. It is a clear yellow to colourless liquid that has a characteristic mercaptan-like odour. It is used as an insecticide and nematicide and it is an acetylcholinesterase inhibitor.
Carbamate poisoning is poisoning due to exposure to carbamates, which are commonly sold as pesticides around the world. In most respects, it is similar to organophosphate poisoning, though typically less severe or requiring a larger amount of the chemical before symptoms appear.