2763-96-4 Usage
Chemical Description
Muscimol is a potent agonist of the GABA receptor, while 4-PIOL is a selective agonist of the GABA(A) receptor.
Description
Muscimol is a potent but toxic structural analogue of γ-aminobutyric acid (GABA), featuring a zwitterionic structure that enables it to cross the blood-brain barrier. It is an inhibitory neurotransmitter that acts through GABAA and GABAC receptors, as well as a G protein-coupled receptor, GABAB. Muscimol is a full GABAA agonist and partial GABAC agonist, with effects on memory formation and retrieval, and it also attenuates airway constriction in guinea pigs. It is a tan solid and has been isolated from mushrooms of the genus Amanita.
Uses
1. Used in Pharmaceutical Research:
Muscimol is used as a molecular probe for studying GABA receptors, which helps in understanding the mechanisms of inhibitory neurotransmission and the development of potential therapeutic agents targeting these receptors.
2. Used in Neuroscience:
Muscimol is used as a research tool in neuroscience to investigate the role of GABAergic systems in various brain functions, including memory and learning processes.
3. Formerly used in Medicine:
Muscimol was formerly used as a sedative and an anti-emetic, although its potent and toxic nature has limited its clinical applications.
4. Used in Toxicology:
Muscimol serves as an example of a toxic compound found in certain mushrooms, which is important for understanding the risks associated with mushroom consumption and the development of antidotes or treatments for mushroom poisoning.
Synthesis Reference(s)
The Journal of Organic Chemistry, 48, p. 4307, 1983 DOI: 10.1021/jo00171a030Synthetic Communications, 12, p. 1089, 1982 DOI: 10.1080/00397918208065973
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 .
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.]
Check Digit Verification of cas no
The CAS Registry Mumber 2763-96-4 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,7,6 and 3 respectively; the second part has 2 digits, 9 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 2763-96:
(6*2)+(5*7)+(4*6)+(3*3)+(2*9)+(1*6)=104
104 % 10 = 4
So 2763-96-4 is a valid CAS Registry Number.
InChI:InChI=1/C4H6N2O2/c5-2-3-1-4(7)6-8-3/h1H,2,5H2,(H,6,7)/p+1
2763-96-4Relevant articles and documents
The Synthesis and Evaluation of Fluoro-, Trifluoromethyl-, and Iodomuscimols as GABA Agonists
Abdul Manan, Mohd Abdul Fatah,Cordes, David B.,Slawin, Alexandra M. Z.,Bühl, Michael,Liao, Vivian W. Y.,Chua, Han. C.,Chebib, Mary,O'Hagan, David
, p. 10848 - 10852 (2017)
Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C-4 fluorine-containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor.
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Frater-Schroeder,M. et al.
, p. 720 - 724 (1969)
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Structure elucidation of pantherine, a flycidal alkaloid from Amanita pantherina (DC.) FR.
Konda,Takahashi,Onda
, p. 1083 - 1087 (2007/10/02)
Pantherine is identified as 5-aminomethyl-3-hydroxyisoxazole by means of spectroscopic experiments and chemical correlation with synthetic compounds.
