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| Names | |
|---|---|
| IUPAC name 2,5-Anhydro-1,4,6-trideoxy-6-(trimethylazaniumyl)-D-ribo-hexitol | |
| Systematic IUPAC name 1-[(2S,4R,5S)-4-Hydroxy-5-methyloxolan-2-yl]-N,N,N-trimethylmethanaminium | |
| Other names L-(+)-muscarine, muscarin, (2S,4R,5S)-(4-hydroxy-5-methyl-tetrahydrofuran-2-ylmethyl)-trimethyl-ammonium | |
| Identifiers | |
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3D model (JSmol) | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.005.541 |
| UNII | |
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| Properties | |
| C9H20NO2+ | |
| Molar mass | 174.26 g/mol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Muscarine,L-(+)-muscarine, ormuscarin is anatural product found in certainmushrooms, particularly inInocybe andClitocybe species, such as the deadlyC. dealbata. Mushrooms in the generaEntoloma andMycena have also been found to contain levels of muscarine which can be dangerous if ingested. Muscarine has been found in harmless trace amounts inBoletus,Hygrocybe,Lactarius andRussula. Trace concentrations of muscarine are also found inAmanita muscaria, though the pharmacologically more relevant compound from this mushroom is theZ-drug-like alkaloidmuscimol.A. muscariafruitbodies contain a variable dose of muscarine, usually around 0.0003% fresh weight. This is very low and toxicity symptoms occur very rarely.Inocybe andClitocybe contain muscarine concentrations up to 1.6%.[1]
Muscarine is a selectiveagonist of themuscarinic acetylcholine receptors.
The namemuscarine derives from that ofAmanita muscaria, from which it was first isolated, by German chemistsOswald Schmiedeberg and Richard Koppe at theUniversity of Tartu, who reported their findings in 1869.[2] The mushroom'sspecific name in turn comes from theLatinmusca for fly because the mushroom was often used to attract and catch flies, hence its common name, "fly agaric".
Muscarine was the firstparasympathomimetic substance ever studied and causes profound activation of theperipheralparasympathetic nervous system that may end in circulatory collapse and death. Being aquaternary ammonium salt, muscarine is less completely absorbed from thegastrointestinal tract than tertiary amines, and it does not cross theblood–brain barrier.[3]Muscarinic agonists activate muscarinic receptors while nicotinic agonists activate nicotine receptors. Both are direct-actingcholinomimetics; they produce their effects by binding to and activatingcholinergic receptors.Final proof of the structure was given by Franz Jellinek and colleagues in 1957 with the help ofX-ray diffraction analysis;[4] Jellinek further described the three-dimensional structure of the molecule using muscarine chloride.[5] These new findings set into motion research on the pharmacology of muscarine and muscarine-like substances that are structurally related toacetylcholine.
Muscarine mimics the function of the natural neurotransmitter acetylcholine in the muscarinic part of the cholinergic nervous system, despite the less flexible structure due to the five-membered ring in the molecular skeleton. With the exception of the double bonded oxygen, all of the acetylcholine structure is present in the right bottom side of muscarine (seeFigure 3 below for comparison of both structures).[6]
There are two mirror forms of muscarine, named: 2S-muscarine and 2R-muscarine.
The scheme below represents a very efficient way of the synthesis of (+)-muscarine according to the scientists Chan and Li in the Canadian journal of Chemistry in 1992.[7]S-(−)-Ethyl lactate (2)(Figure 4) is converted into the 2,6-dichlorobenzyl ether (3).Diisobutylaluminium hydride (DIBAL) reduction of the 2,6-dichlorobenzyl ether gives thealdehyde (4). Treatment of the crude aldehyde with allyl bromide and zinc powder in water with NH4Cl as catalyst resulted in an anti:syn mixture of 5a and 5b. Treatment of 5a with iodine in CH3CN at 0 °C gives the cyclized product 6a. Finally treatment of 6a with excess trimethylamine in ethanol gave (+)-muscarine (2S,4R,5S). A similar reaction sequence with 5b gave (+)-epimuscarine (7).[7]
-muscarin.gif)
It can be synthesized in various ways from completely different substances,[8][9][10][11][12][13][14][15][16][17] particularly from 2,5-dimethyl-3-carboxymethyl flurane.
Muscarine mimics the action of theneurotransmitteracetylcholine byagonisingmuscarinic acetylcholine receptors. These receptors were named after muscarine, to differentiate them from the otheracetylcholine receptors (nicotinic receptors), which are comparatively unresponsive to muscarine. There are five different types of muscarinic receptors:M1,M2,M3,M4 andM5. Most tissues express a mixture of subtypes.
The M2 and M3 subtypes mediate muscarinic responses atperipheral autonomic tissues. M1 and M4 subtypes are more abundant inbrain andautonomic ganglia.
The odd numbered receptors, M1, M3 and M5, interact withGq proteins to stimulate phosphoinositide hydrolysis and the release of intracellular calcium. Conversely, the even numbered receptors, M2 and M4, interact withGi proteins to inhibit adenylyl cyclase, which results in a decrease of intracellular concentration of cyclic adenosine monophosphate (cAMP).
Most agonists for muscarine receptors are not selective for subtypes.[18]
Muscarinic receptors also signal via other pathways, for instance viaG beta-gamma complex modulation ofpotassium channels. This allows muscarine to modulate cellular excitability via themembrane potential.
A paucity of research exists on the metabolism of muscarine in the human body, suggesting this compound is not metabolized by humans. Though there has been extensive research in the field of acetylcholine metabolism byacetylcholinesterase, muscarine is not metabolized by this enzyme, partly explaining the compound's potential toxicity. Muscarine is readily soluble in water. The most likely way for muscarine to leave the blood is via renal clearance; it will eventually leave the body in urine.[19]
 | This sectionneeds morereliable medical references forverification or relies too heavily onprimary sources. Please review the contents of the section andadd the appropriate references if you can. Unsourced or poorly sourced material may be challenged andremoved.Find sources: "Muscarine" – news ·newspapers ·books ·scholar ·JSTOR(November 2019) |  |
Muscarinic agonists are used as drugs in treatingglaucoma, postoperativeileus, congenitalmegacolon,urinary retention andxerostomia. Muscarine iscontraindicated in people with diseases that make them susceptible to parasympathetic stimulation, people who haveasthma orCOPD, or people who havepeptic ulcer disease. Also people with an obstruction in thegastrointestinal orurinary tract are not prescribed muscarine because it will aggravate the obstruction, causing pressure to build up that may lead to perforation.
As muscarine works on themuscarinic acetylcholine receptor, the best comparison can be made with acetylcholine, which normally works on this receptor. Pure muscarine compared to pure acetylcholine is stated in most cases to be more potent, its action is always slower but longer lasting than acetylcholine. A possible explanation for this long-lasting behavior might be that muscarine does not get hydrolyzed by acetylcholinesterase in the synaptic cleft.[20]
Muscarine poisoning is characterized bymiosis, blurred vision, increasedsalivation, excessivesweating,lacrimation, bronchial secretions, bronchoconstriction,bradycardia, abdominal cramping, increased gastric acid secretion, diarrhea andpolyuria. If muscarine reaches the brain it can causetremor,convulsions andhypothermia.Cardiac ventricles containmuscarinic receptors that mediate a decrease in the force of contractions leading to a lower blood pressure. If muscarine is administered intravenously, muscarine can trigger acutecirculatory failure withcardiac arrest.[1]
The symptoms of intoxication with mushrooms rich in muscarine, especiallyInocybe, are very typical:
The symptoms start early, after one-quarter to two hours, with headache, nausea, vomiting, and constriction of thepharynx. Then salivation, lacrimation, and diffuse perspiration set in, combined with miosis, disturbedaccommodation, and reduced vision. Gastric and small bowelcolic leads to diarrhea, and there is a painful urge for urination.Bronchoconstriction leads to asthmatic attacks and severedyspnea, and bradycardia combined with markedhypotension andvasodilation results incirculatory shock. Death after 8 to 9 hours has been reported in about 5% of the cases, but can be avoided completely by prompt administration of IV or IManticholinergic drugs.[21]
Antimuscarinics such asatropine can be used as anantidote to muscarine. Atropine is, like muscarine, an alkaloid but unlike muscarine is an antagonist of the muscarinic receptors. Hence, it inhibits the effects of acetylcholine.
Muscarinic antagonistsdilate the pupil and relax the ciliary muscle, are used in treatment of inflammatory uveitis and is associated with glaucoma. They are also used to treat urinary incontinence and diseases characterized by bowel hypermotility such asirritable bowel syndrome.
Muscarinic antagonists are often calledparasympatholytics because they have the same effect as agents that block postganglionic parasympathetic nerves.
PoisonousAmanita mushrooms | |||||||||||||||||||||||||||||||||||||
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| Subgenus Amanita |
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| Subgenus Amanitina |
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