Muscarine

Alexandra Milsom University of Wales College of Medicine, Cardiff, United Kingdom

ã 2007 Elsevier Inc. All rights reserved.

Introduction

Muscarine is the prototypical muscarinic agonist. It is a toxic alkaloid found in Amanita

muscaria (fly agaric) and other fungi of the Inocybe and Clitocybe species (e.g., Inocybe geophylla,
Clitocybe dealbata) Sweetman (2002), Hughes et al (1966), Catalfomo and Eugster (1970).
Muscarine was the first parasympathomimetic substance ever studied and causes pro-
found parasympathetic activation that may end in convulsions and death. The specific
antidote is atropine Sweetman (2002).

Nomenclature
Name of the Clinical
Form
Related Names dextro muscarine; dl muscarine; levo muscarine; muscarin;
Source: EMTREE muskarin; (+)-(2s,4R,5S)-Muscarine; (+)-Muscarine;
ammonium, trimethyl(tetrahydro-4-hydroxy-5-
methylfurfuryl)-; L-(+)-Muscarine
Chemical Names 2-Methyl-3-hydroxy-5-(aminomethyl)tetrahydrofuran,
trimethylammonium salt
CAS Number 300-54-9

Basic Chemistry
Chemical Structure
Structure

Comments Muscarine is a quaternary trimethyl ammonium salt of 2-methyl-3-oxy-

5-(amino)-tetrahydrofuran. It contains a quaternary nitrogen
important for action at the anionic site of the receptor (an aspartate
residue in transmembrane domain III).
Chemical C9 H20 N O2
Formula
Properties

1
2 Muscarine

Physical Melting point: 180-181 C; extremely hygroscopic Budavari (2001). This

Properties information refers to muscarine chloride: C9H20NO.2Cl, MW: 209.75.
Potentially toxic.
Molecular 174.262
Weight
Solubility Aqueous solutions of muscarine chloride are stable. Muscarine
chloride is very soluble in water and ethanol; slightly soluble in
chloroform, ether, and acetone Budavari (2001).

Targets-Pharmacodynamics

Muscarinic receptors are 7-transmembrane receptors and mediate their responses by

activating a cascade of intracellular pathways.

Target Name(s):
M1 Muscarinic Acetylcholine Receptor
M2 Muscarinic Acetylcholine Receptor
M3 Muscarinic Acetylcholine Receptor
M4 Muscarinic Acetylcholine Receptor
M5 Muscarinic Acetylcholine Receptor

Therapeutics

Muscarine has no clinical uses. Its lethal dose in humans has been estimated to be 40-180
mg Herman and Chyka (2004).

Adverse Effects
Muscarine is potentially toxic. Ingestion can cause symptoms similar to cholinergic
poisoning, including excess perspiration, salivation and lacrimation, bradycardia, miosis,
blurred vision, abdominal pain, diarrhea, hypotension, and pulmonary congestion. Treat-
ment with atropine (1 to 2 mg intramuscularly every 30 minutes) effectively blocks these
effects Brown and Taylor (2001).

Pre-Clinical Research

Intravenous injection of small doses of muscarine leads to a marked fall in blood pressure
and a slowing or temporary cessation of the heartbeat in various species Brown and Taylor
(2001).

Pharmacokinetics
Various species

Prep. and
Route of
Value Units Admin. Reference Comments

Absorption
Bioavailability
Distribution
 Muscarine 3

Volume of Herman and Because it is a

Distribution Chyka (2004) quaternary salt,
muscarine does not
readily cross the
blood-brain barrier.
Plasma Protein
Binding
Metabolism
Plasma Half-Life
Bio Half-Life Fraser (1957) It is not metabolized
by cholinesterase
and, therefore, has a
long biological half-
life.
Clearance
Routes of
Elimination

Potency

Prep.
and
Route Cell Exp.
Organ/ of Line/ End
Value Units Tissue Admin. Type Effects Point Reference Comments

Mouse
LD50 0.23 mg/kg i.v. Fraser
(1957)

Other Research
Muscarine had been employed for many years because it has a very selective excitatory
effect on the effector cells of tissues innervated by postganglionic cholinergic nerves. It
does not stimulate nicotinic receptors of autonomic ganglia or skeletal muscle as does
acetylcholine Booth and McDonald (1982).
Synthesis:
Whiting et al (1972)
Mubarak and Brown (1980)

Other Information – Web Sites

FDA: Mushroom toxins: The Bad Bug Book. US Food and Drug Administration. 2000.
Available at http://www.fda.gov/-Useful information regarding mushroom toxicity,
including symptoms and treatment.
Open access. Herman, M. and Chyka, P. Toxicity, Mushrooms-Muscarine. 2004.
Available at http://www.emedicine.com/-medical information site. Free registration
required.
4 Muscarine

Journal Citations

Fraser, P.J., 1957. Pharmacological actions of pure muscarine chloride. Br. J. Pharmacol., 12, 47–52.
Hughes, D.W., Genest, K., Rice, W.B., 1966. The occurrence of muscarine in Clitocybe dealbata. Lloydia,
29(4), 328–332.
Catalfomo, P., Eugster, C.H., 1970. Muscarine and muscarine isomers in selected Inocybe species. Helv.
Chim. Acta., 53(4), 848–851.
Whiting, 1972. Can. J. Chem., 50, 3322.
Mubarak, A.M., Brown, D.M., 1980. A simple stereospecific synthesis of (+)-muscarine. Tetrahedron
Letters, 21, 2453.

Book Citations

Sweetman, S.C., 2002. Supplementary Drugs and Other Substances. Sweetman, S.C. (Ed.), Martindale:
The complete drug reference, Edition 33, pp. 1638–1639, Pharmaceutical Press, London.
Budavari, S., 2001. Budavari, S. (Ed.), The Merck Index: An encyclopedia of chemicals, drugs, and
biologicals, Edition 13, p. 6338, Merck Research Laboratories, Whitehouse Station, NJ.
Booth, N.H., McDonald, L.E., 1982. Booth, N.H., McDonald, L.E. (Ed.), Veterinary Pharmacology and
Therapeutics, Edition 5, p. 3; 119, Iowa State University Press, Ames, IA.
Brown, J.H., Taylor, P., 2001. Muscarinic Receptor Agonists and Antagonists. Gilman, A.G., Limbird, L.E.
(Ed.), Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Edition 10, pp. 155–173,
McGraw Hill, New York.
Herman, M., Chyka, P., 2004. Toxicity, Mushrooms-Muscarine. . http://www.emedicine.com/.