Mushroom Muscarine

Mushrooms, Muscarine, Pages 172-173, Anthony S. Manoguerra SummaryPlus Full Text + Links PDF (53 K)... 

Muscarine is a poisonous substance present in the mushroom Amanita muscana Its struc ture IS represented by the constitution shown here... 

Muscarine, an alkaloid from certain species of mushrooms, is a muscarinic receptor agonist. The compound has toxicologic importance muscarine poisoning will produce all of the effects that are associated with an overdose of ACh (e.g., bronchocon strict ion, bradycardia, hypotension, excessive salivary and respiratory secretion, and sweating). Poisoning by muscarine is treated with atropine. 

The following factors have been suggested as alternatives to consider when presented with a potential case of exposure to nerve agents carbamate and organophosphate pesticides alkaloids such as nicotine or coniine ingestion of mushrooms containing muscarine and... 

From recent literature it must be coneluded that mushrooms of the genera Inocybe and Clitocybe contain toxic components that are different from muscarine. The severe symptoms reported of an Israeli ehild poisoned with /. tristis therefore departed from what is known of musearine poisoning (Amitai et al., 1982). The toxic activities of C. acromelalga and C. amoenolens, two Clitocybe species containing clitidine and acromelic acid A, respectively, were studied in rats (Fukuwatari et al., 2001 Saviuc et al., 2003). 

This mushroom known as Jack 0 Lantern, can cause severe gastroenteritis after a latent period of one to three hours, with headache, nausea, sweating, vomiting, abdominal pain, sometimes associated with bitter taste, and a feeling of coldness. It has been argued that these elfects may be due to a muscarine-like reaction, but no muscarine has been identified. A sesquiterpene, illudin S, is believed to be at least one of the toxic components. 

Note that it shares some structural features with the acetylcholine molecule. Specifically, both molecules possess an oxygen atom separated by two methylene (-CH2-) groups from a positively charged nitrogen atom. Muscarine was isolated from Amanita muscaria, a poisonous mushroom, more than a century ago. Muscarine causes sweating and pupillary constriction. These are some of the same effects that are caused by acetylcholine itself, confirming that muscarine is an acetylcholine agonist. 

Another well-known hallucinogen is psilocybin from the mushroom genus Psilocyhe Fig. 11.13). Muscarine is an isoxazole derivative (Fig. 11.13). Table 11.3 lists some of the hallucinogens in plants. 

The muscarinic ACh receptors (of which there are at least five subtypes) are metabotropic. Their name is derived from the alkaloid muscarine, which is found in the fly agaric mushroom (Amanita muscaria), for example. Like ACh, muscarine is bound at the receptor, but in contrast to ACh (see C), it is not broken down and therefore causes permanent stimulation of muscle. 

Muscarine is a natural alkaloid that is found in a number of wild mushrooms. Despite the fact that muscarine does not have any therapeutic value, it is of interest because of its expressed toxic properties, which made it one of the first systematically studied cholinomimetic substances. This compound was an underlying classification of cholinergic muscarinic receptors. The action of muscarine is similar to that of acetylcholine on peripheral autonomic effector organs, and atropine is an antagonist to it. Unlike acetylcholine, muscarine does not act on nicotinic receptors. 

Mushroom poisoning requires serious medical intervention because muscarine absorbs well in the gastrointestinal tract, and therefore it can lead to death. Muscarine is considerably more powerful than acetylcholine, possibly because of its high stability. Because it is... 

Antidotes for poisoning by cholinergic drugs Atropine is used for poisoning by organophosphorus insecticides, chemical warfare nerve gases, and as an antidote for mushroom poisoning caused by muscarine in certain species, such as Amanita muscaria. 

Stimulation - excitatory amino acids -headache, confusion, hallucinations Red alga (red tide), Green alga Mushrooms - Amanita family (fly agaric), flat pea [Lathyrus] Kainic acid, domoic acid -concentrated in shellfish, Ibotenic acid, muscarinic acid, (hallucinations) Latthyrism - motor neuron degeneration... 

Plants containing indoleamines include Psilocybe mushrooms, morning glory and Virola. Plants containing tropane alkaloids such as the muscarinic antagonists scopolamine and atropine are found in some members of the Solanaceae plant family—including datura, mandrake, henbane and... 

Classical studies by Sir Henry Dale demonstrated that the receptors activated by muscarine, an alkaloid isolated from the mushroom Amanita muscaria, are the same receptors activated by ACh released from parasympathetic nerve endings, from which the general notion that muscarinic agonists have parasympathomimetic properties was born. This conclusion is true but incomplete, and we now know that muscarinic receptors have a broader distribution and many functional roles. To understand the actions of cholinomimetic drugs it is essential to recognize that muscarinic receptors (1) mediate the activation of effectors by ACh released from parasympathetic nerve... 

Pilocarpine is a naturally occurring cholinomimetic alkaloid that is structurally distinct from the choline esters. It is a tertiary amine that crosses membranes relatively easily. Therefore, it is rapidly absorbed by the cornea of the eye, and it can cross the blood-brain barrier. Pilocarpine is a pure muscarinic receptor agonist, and it is unaffected by cholinesterases. Muscarine is an alkaloid with no therapeutic use, but it can produce dangerous cholinomimetic stimulation following ingestion of some types of mushrooms (e.g., Inocybes). 

Atropine is used as an antidote in poisoning by an overdose of a cholinesterase inhibitor (see Chapter 14). It also is used in cases of poisoning from species of mushroom that contain high concentrations of muscarine and related alkaloids (e.g., Clitocybe dealbata). 

Other cholinergic agonists have no therapeutic use. Muscarine (4.3) is an alkaloid of the mushroom Anumita muscaria muscarone (4.9) is its semisynthetic analog. Pilocarpine (2.2) is found in the leaves of a shrub and can be used to increase salivation or sweating. Arecoline (4.10) is also an alkaloid, and occurs in the betel nut that is used as a mild euphoriant in India and Southeast Asia. Finally, oxotremorine (4.11) is a synthetic experimental agent that produces tremors and is helpful in the study of antiparkinsonian drugs. 

Muscarine Muscarine, molecular formula C9H2qN02, first isolated from fly agaric Amanita muscaria, occurs in certain mushrooms, especially in the species of the genera Inocybe and Clitocybe. It is a parasympathomimetic substance. It causes profound activation of the peripheral parasympathetic nervous system, which may result in convulsions and death. Muscarine mimics the action of the neurotransmitter acetylcholine at the muscarinic acetylcholine receptors. 

Acetylcholine (ACh) is an example of an endogenous neurotransmitter that binds to more than one receptor type, the nicotinic acetylcholine receptor (nAChR) which preferentially binds nicotine and the muscarinic receptor which binds muscarine, a mushroom alkaloid. The latter is a G protein-coupled receptor while the nACh receptor is an excitatory ligand-gated ion channel that transports Na-i- ions. Nicotinic cholinergic receptors are found in the CNS, autonomic ganglia, and at the neuromuscular junction of skeletal muscles. They are a possible target for anaesthetics. 

The tertiary natural cholinomimetic alkaloids (pilocarpine, nicotine, lobeline Figure 7-3) are well absorbed from most sites of administration. Nicotine, a liquid, is sufficiently lipid-soluble to be absorbed across the skin. Muscarine, a quaternary amine, is less completely absorbed from the gastrointestinal tract than the tertiary amines but is nevertheless toxic when ingested—eg, in certain mushrooms—and it even enters the brain. Lobeline is a plant derivative similar to nicotine. These amines are excreted chiefly by the kidneys. Acidification of the urine accelerates clearance of the tertiary amines. 

Certain mushrooms, especially those of the genus Inocybe, contain muscarinic alkaloids. Ingestion of these mushrooms causes typical signs of muscarinic excess within 15-30 minutes. These effects can be very uncomfortable but are rarely fatal. Treatment is with atropine, 1-2 mg parenterally. (Amanita muscaria, the first source of muscarine, contains very low concentrations of the alkaloid.)... 

A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects. Many of them have other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures tricyclic antidepressants, which have anticholinergic, quinidine-like, and a-blocking effects, can cause severe cardiovascular toxicity. 

The Amanita muscaria mushroom from which muscarine is isolated is also psychoactive. It was believed at first that muscarine was the primary CNS agent. However, more detailed research indicated that muscarine only constituted 0.003% of the fungus. Other species of Inocybe and Clitocybe have more muscarine than muscaria. Other isoxazole components of the muscaria mushroom, such as ibotenic acid and its metabolites, are the main causes of amanita intoxication. This mushroom is believed to have been involved in ancient rituals of the Old World, especially in the Ayrian culture which lived in Siberia around 2000 B.C. This rite worshipped a god called Soma whose presence on earth occurred in the mushroom. Amanita muscaria. Rituals involved brewing a juice with the mushrooms which was consumed by priests. Their urine (isoxazole metabolites) was collected and drunk by others. This ceremony could involve many people and several metabolic rounds until everyone was intoxicated. 

L(+)-Muscarine, a cholinergic agonist from the mushroom Amanita muscaria... 

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