Muscarine

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. Muscarine is only a trace compound in the fly agaric Amanita muscaria; the pharmacologically more relevant compounds from this mushroom are ibotenic acid and 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%.Figure 1. The structural formula of 2S-muscarine.Figure 2. The structural formula of 2R-muscarine.Figure 3. Acetylcholine for comparison. 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. Muscarine is only a trace compound in the fly agaric Amanita muscaria; the pharmacologically more relevant compounds from this mushroom are ibotenic acid and 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%. Muscarine is a nonselective agonist of the muscarinic acetylcholine receptors. Muscarine was first isolated from Amanita muscaria by German chemists Oswald Schmiedeberg and Richard Koppe in University of Dorpat, who reported their findings in 1869. It was the first parasympathomimetic substance ever studied and causes profound activation of the peripheral parasympathetic nervous system that may end in circulatory collapse and death. Being a quaternary ammonium salt, muscarine is less completely absorbed from the gastrointestinal tract than tertiary amines, and it does not cross the blood-brain barrier.Muscarinic agonists activate muscarinic receptors while nicotinic agonists activate nicotine receptors. Both are direct-acting cholinomimetics; they produce their effects by binding to and activating cholinergic receptors.Final proof of the structure was given by Franz Jellinek and colleagues in 1957 with the help of X-ray diffraction analysis; Jellinek further described the three-dimensional structure of the molecule using muscarine chloride. These new findings set into motion research on the pharmacology of muscarine and muscarine-like substances that are structurally related to acetylcholine. 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 (see Figure 3 below for comparison of both strtuctures).