MUSCIMOL

Description

The amino acid γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter that acts through two families of heteromeric ligand-gated ion channels, GABA_A and GABA_C and a G protein-coupled receptor, GABA_B. Muscimol is a full GABA_A agonist and partial GABA_C agonist. It binds GABA_A on both high- and low-affinity sites (K_d = 10 and 270 nM, respectively), stimulating chloride efflux with an EC₅₀ value of 200 nM. Benzodiazepines enhance the effects of muscimol via GABA_A without altering its binding. Muscimol activates GABA_C receptors with an EC₅₀ value of 1.3 μM. It also acts as an inhibitor of GABA_A uptake and a substrate for the GABA-metabolizing enzyme GABA transaminase. Muscimol impairs memory formation and retrieval in mice and attenuates airway constriction in guinea pigs in vivo.

Chemical properties

Tan Solid

The Uses of MUSCIMOL

A potent but toxic structural analogue of g-aminobutyric acid (GABA), with a zwitterionic structure that can cross the blood-brain barrier

The Uses of MUSCIMOL

As a molecular probe to study GABA receptors.

What are the applications of Application

Muscimol is a potent and specific GABAA receptor agonist/GABA analog

Definition

ChEBI: A member of the class of isoxazoles that is 1,2-oxazol-3(2H)-one substituted by an aminomethyl group at position 5. It has been isolated from mushrooms of the genus Amanita.

Synthesis Reference(s)

The Journal of Organic Chemistry, 48, p. 4307, 1983 DOI: 10.1021/jo00171a030
Synthetic Communications, 12, p. 1089, 1982 DOI: 10.1080/00397918208065973

General Description

Crystals. Formerly used as a sedative and an anti-emetic.

Reactivity Profile

MUSCIMOL is a ketone and an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides

Health Hazard

MUSCIMOL is a natural constituent of amanita mushrooms and is extremely toxic. It is a potent central nervous system depressant, and is believed to be responsible for most of the nervous system effects that result from eating this mushroom. The lowest toxic dose in humans has been reported at 109 mg/kg.

Health Hazard

Muscimol is a toxic alkaloid of poisonousmushroom species, producing neurologicaction. It is a potent depressant of thecentral nervous system. The adverse healtheffects from its ingestion include sleep,hallucination, distorted perceptions, andvomiting.
LD50 value, oral (mice): 17 mg/kgLD50 value, intraperitoneal (mice): 2.5 mg/kg.

Fire Hazard

When heated to decomposition, MUSCIMOL emits toxic fumes of nitrogen oxides.

Biological Activity

Potent GABA A receptor agonist and partial GABA C receptor agonist. Inhibits memory retention and attenuates airway constriction in vivo .

Potential Exposure

Formerly used as a sedative and as anantiemetic; and for experimental laboratory purposes.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Speed in removing material from skinis of extreme importance. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions,including resuscitation mask) if breathing has stopped andCPR if heart action has stopped. Transfer promptly to amedical facility. When this chemical has been swallowed,get medical attention. Give large quantities of water andinduce vomiting. Do not make an unconscious personvomit.

storage

Room temperature

Purification Methods

Recrystallise muscimol from MeOH/tetrahydrofuran or EtOH and sublime it at 110-140o (bath) at 10-4 mm to give a yellow spot with ninhydrin which slowly turns purple [NMR: Bowden et al. J Chem Soc (C) 172 1968]. It can also be purified by dissolving in the minimum volume of hot H2O and adding EtOH dropwise until cloudy, cool, and colourless crystals separate; IR: max 3445w, 3000-2560w br, 2156w, 1635s and 1475s cm-1. [NMR: Jager & Frey Justus Liebigs Ann Chem 817 1982.] Alternatively it has been purified by two successive chromatographic treatments on Dowex-1 x 8, with the first elution with 2M AcOH and a second with a linear gradient between 0—2M AcOH, evaporating the desired fractions and recrystallising the residue from MeOH. [McCarry & Savard Tetrahedron Lett 22 5153 1981, Nakamura Chem Pharm Bull Jpn 19 46 1971.]