Muscimol
IUPAC name	5-(aminomethyl)- isoxazol-3-ol
Identifiers
CAS number	18174-72-6
SMILES	NCc1cc(O)no1
ChemSpider ID	4116
Properties
Molecular formula	C4H6N2O2
Molar mass	114.10 g/mol
Melting point	184-185°C
Solubility in water	very soluble
Solubility in ethanol	slightly soluble
Solubility in methanol	very soluble
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Muscimol (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 GABA_A receptor.

[edit] Chemistry

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.

[edit] Biology

Muscimol is produced naturally in the mushrooms Amanita muscaria, Amanita pantherina, and Amanita gemmata, along with muscarine, muscazone, and ibotenic acid.^[1][2] A. muscaria and A. pantherina are not considered safe for human consumption, poisonings have occurred from A. muscaria and A. pantherina as well.^[3] It is thought that^[who?], in A. muscaria, the layer just below the skin of the cap contains the highest amount of muscimol, and is therefore the most psychoactive portion.

Amanita muscaria, which contains muscimol

[edit] Pharmacology

Muscimol is a potent GABA_A agonist, activating the receptor for the brain's major inhibitory neurotransmitter, GABA. Muscimol actually binds to the same binding site on the GABA_A receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites.^[4] GABA_A 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 GABA_A agonist, it is also a potent partial agonist at the GABA_C receptor, and so its effects profile results from a combined action at both targets.^[5]

During a test involving rabbits connected to an EEG, muscimol showed a distinctly synchronized EEG tracing. This is substantially different from indolic psychedelics, as brainwave patterns will generally show a desynchronization. In higher doses (2mg/kg), the EEG will show characteristic spikes.

When used in vivo, muscimol will pass through the human body, and be excreted (as muscimol) in the subject's urine.

The psychoactive dose of muscimol is around 10-15 mg for a normal person. ^[6]. A Guide to British Psilocybin Mushrooms by Richard Cooper published in 1977 recommends a smaller dose, 8.5mg, and suggests that it is possible for this amount to be present in as little as 1g of dried A.muscaria. It goes on to say that determining a correct dose can be difficult as potency varies dramatically from one mushroom to the next.

[edit] Toxicity

LD50 mice: 3.8 mg/kg s.c, 2.5 mg/kg i.p.^[7]

LD50 rats: 4.5 mg/kg i.v, 45 mg/kg orally.^[7]

[edit] Effects

The effects of muscimol are substantially different from Psilocybe mushroom alkaloids, as the chemicals target separate parts of the brain. Muscimol has been shown to lack "structured" hallucinations in most cases, and the effects are frequently compared to a lucid dream state. The hallucinogenic effect produced by muscimol is most closely comparable to the hallucinogenic side effects produced by some other GABAergic drugs such as zolpidem.

[edit] See also

• Psychedelic drug
• Psychoactive drug
• Amanita muscaria
• Ibotenic acid
• List of Entheogens

[edit] External links

• Psychoactive Amanitas on Erowid

[edit] References

1. ^ Chilton WS, Ott J. Toxic metabolites of Amanita pantherina, A. cothurnata, A. muscaria and other Amanita species. Lloydia. 1976 Mar-Jun;39(2-3):150-7. PMID 985999
2. ^ Michelot D, Melendez-Howell LM. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycological Research. 2003 Feb;107(Pt 2):131-46. PMID 12747324
3. ^ Tupalska-Wilczyńska K, Ignatowicz R, Poziemski A, Wójcik H, Wilczyński G. Poisoning with spotted and red mushrooms--pathogenesis, symptoms, treatment. (Polish). Wiadomosci Lekarskie. 1996;49(1-6):66-71. PMID 9173659
4. ^ Frølund B, Ebert B, Kristiansen U, Liljefors T, Krogsgaard-Larsen P. GABA(A) receptor ligands and their therapeutic potentials. Current Topics in Medicinal Chemistry. 2002 Aug;2(8):817-32. PMID 12171573
5. ^ Woodward RM, Polenzani L, Miledi R. Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists. Molecular Pharmacology. 1993 Apr;43(4):609-25. PMID 8386310
6. ^ Erowid Psychoactive Amanitas Vault : Dosage
7. ^ ^{a b} Erowid Psychoactive Amanitas Vault : Chemistry

• Merck Index, 12th Edition
• Ito Y, Segawa K, Fukuda H. 1995 "Functional diversity of GABAA receptor ligand-gated chloride channels in rat synaptoneurosomes" Synapse 19(3):188-96.
• Rätsch, Christian. (1998). The Encyclopedia of Psychoactive Plants. Rochester, VT: Park Street Press.
• Beaumont K, Chilton W. S., Yamamura H. I., Enna S. J. (1978). "Muscimol binding in rat brain: association with synaptic GABA receptors". Brain Res. 148 (1): 153–62. doi:10.1016/0006-8993(78)90385-2. 
• S. R. Snodgrass (1978). "Use of ³H-muscimol for GABA receptor studies". Nature 273 (1): 392–394. doi:10.1038/273392a0. 
• G. A. R. Johnston, D. R. Curtis, W. C. de Groat and A. W. Duggan (1968). "Central actions of ibotenic acid and muscimol". Biochemical Pharmacology 17 (12): 2488–2489. doi:10.1016/0006-2952(68)90141-X.