Tmic
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Record Information
Version2.0
Creation Date2009-07-03 21:01:06 UTC
Update Date2014-12-24 20:25:31 UTC
Accession NumberT3D2456
Identification
Common NameMuscimol
ClassSmall Molecule
DescriptionMuscimol (Agarin, Pantherine) is the major psychoactive alkaloid present in many mushrooms of the Amanita genus. Unlike psilocybin, a tryptamine, muscimol is a potent, selective agonist of the GABAA receptor. Amanita muscaria contains two main active ingredients, Ibotenic acid and its derivative Muscimol. Muscimol is the product of the decarboxylation or drying of ibotenic acid and it is thought that muscimol is as much as ten times more potent than ibotenic acid. (2)
Compound Type
  • Amine
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3(2H)-Isoxazolone, 5-(aminomethyl)-, monohydrobromide
3-Isoxazolol, 5-(aminomethyl)-, monohydrobromide
3-Isoxazolol, 5-(aminomethyl)-, monohydrobromide (8CI)
5-(Aminomethyl)-3(2H)-isoxazolone
5-(Aminomethyl)-3(2H)-isoxazolone hydrobromide
5-(Aminomethyl)-3-isoxazolol hydrobromide
5-(Aminomethyl)-3-isoxazolol monohydrobromide
5-Aminomethyl-3-hydroxyisoxazole hydrobromide
5-Aminomethyl-3-isoxyzole hydrobromide
Agarin
Agarin hydrobromide
Muscimol hydrobromide
Pantherine
Chemical FormulaC4H6N2O2
Average Molecular Mass114.103 g/mol
Monoisotopic Mass114.043 g/mol
CAS Registry Number18174-72-6
IUPAC Name5-(aminomethyl)-1,2-oxazol-3-ol
Traditional Namemuscimol
SMILESNCC1=CC(O)=NO1
InChI IdentifierInChI=1S/C4H6N2O2/c5-2-3-1-4(7)6-8-3/h1H,2,5H2,(H,6,7)
InChI KeyInChIKey=ZJQHPWUVQPJPQT-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic nitrogen compounds
Sub ClassOrganonitrogen compounds
Direct ParentAralkylamines
Alternative Parents
Substituents
  • Aralkylamine
  • Azole
  • Isoxazole
  • Heteroaromatic compound
  • Lactam
  • Organoheterocyclic compound
  • Oxacycle
  • Azacycle
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Primary aliphatic amine
  • Organic oxide
  • Organopnictogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point184-185°C
Boiling PointNot Available
SolubilitySolubility in water: very soluble Solubility in ethanol: slightly soluble Solubility in methanol: very soluble
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility57.9 g/LALOGPS
logP-0.95ALOGPS
logP-1.4ChemAxon
logS-0.29ALOGPS
pKa (Strongest Acidic)5.78ChemAxon
pKa (Strongest Basic)7.46ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.28 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity28.15 m³·mol⁻¹ChemAxon
Polarizability10.53 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-003r-9000000000-8a5c7c8119385828f867View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014i-3900000000-68483046cfeb7ca5d01bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0002-9000000000-6de63da45a13d454cce3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00kb-9000000000-6b5110dcd6fa6b4422e8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014i-9000000000-c2fbac7befc44bdfbe43View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014r-9000000000-f4eda66dfcf7c0a3918cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-3900000000-b58c956f64f0f049a64cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014j-9600000000-164169f85b3f6f6c94dbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-100u-9000000000-04ba67371609e08956eeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-3900000000-2b5bf5ca3739d495ccc9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-9800000000-ac88ce1ff672c846f8b9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-2bbb93920e5a57deff3aView in MoNA
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (1)
Mechanism of ToxicityMuscimol is a potent GABAA agonist, activating the receptor for the brain's major inhibitory neurotransmitter, GABA. Muscimol actually binds to the same binding site on the GABAA receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites. GABAA receptors are widely distributed in the brain, and so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex, hippocampus, and cerebellum. However while muscimol is conventionally thought of as a selective GABAA agonist, it is also a potent partial agonist at the GABAC receptor, and so its effects profile results from a combined action at both targets. (2)
MetabolismNot Available
Toxicity ValuesLD50: 3.8 mg/kg (Subcutaneous, Mouse) (2) LD50: 2.5 mg/kg (Intraperitoneal, Mouse) (2) LD50: 4.5 mg/kg (Intravenous, Rat) (2) LD50: 45 mg/kg (Oral, Rat) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMuscimol is produced naturally in the mushrooms Amanita muscaria, Amanita pantherina, and Amanita gemmata, along with muscarine, muscazone, and ibotenic acid. (2)
Minimum Risk LevelNot Available
Health EffectsMuscimol is neurotoxic and produces hallucinations. (2)
SymptomsMuscimol is hallucinogenic. (2)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID205536
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID25520
BioCyc IDNot Available
CTD IDNot Available
Stitch IDMuscimol
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkMuscimol
References
Synthesis ReferenceNot Available
MSDST3D2456.pdf
General References
  1. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  2. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
  3. Wikipedia. Mushroom poisoning. Last Updated 10 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA2
Uniprot ID:
P47869
Molecular Weight:
51325.85 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA4
Uniprot ID:
P48169
Molecular Weight:
61622.645 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Transporter activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA5
Uniprot ID:
P31644
Molecular Weight:
52145.645 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA6
Uniprot ID:
Q16445
Molecular Weight:
51023.69 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRG1
Uniprot ID:
Q8N1C3
Molecular Weight:
53594.49 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRG2
Uniprot ID:
P18507
Molecular Weight:
54161.78 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRG3
Uniprot ID:
Q99928
Molecular Weight:
54288.16 Da
References
  1. Wikipedia. Muscimol. Last Updated 5 June 2009. [Link]
General Function:
Gaba-a receptor activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission.
Gene Name:
GABRR2
Uniprot ID:
P28476
Molecular Weight:
54150.41 Da
References
  1. Tomaszewska-Zaremba D, Mateusiak K, Przekop F: The role of GABA(A) receptors in the neural systems of the medial preoptic area in the control of GnRH release in ewes during follicular phase. Anim Reprod Sci. 2003 May 15;77(1-2):71-83. [12654529 ]
General Function:
G-protein coupled gaba receptor activity
Specific Function:
Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
Gene Name:
GABBR1
Uniprot ID:
Q9UBS5
Molecular Weight:
108319.4 Da
References
  1. Belozertseva IV, Andreev BV: [A pharmaco-ethological study of the GABA-ergic mechanisms regulating the depression-like behavior of mice]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997 Nov-Dec;47(6):1024-31. [9472168 ]