Muscimol

Muscimol

Names
IUPAC name 5-(Aminomethyl)-isoxazol-3-ol
Identifiers
CAS Number	2763-96-4 N
ChEBI	CHEBI:7035 N
ChEMBL	ChEMBL273481 Y
ChemSpider	4116 Y
IUPHAR/BPS	4259
Jmol 3D model	Interactive image
PubChem	4266
InChI InChI=1S/C4H6N2O2/c5-2-3-1-4(7)6-8-3/h1H,2,5H2,(H,6,7) Y Key: ZJQHPWUVQPJPQT-UHFFFAOYSA-N Y InChI=1/C4H6N2O2/c5-2-3-1-4(7)6-8-3/h1H,2,5H2,(H,6,7) Key: ZJQHPWUVQPJPQT-UHFFFAOYAI
SMILES O=C1/C=C(\ON1)CN
Properties
Chemical formula	C4H6N2O2
Molar mass	114.10 g·mol−1
Melting point	184 to 185 °C (363 to 365 °F; 457 to 458 K)
Solubility in water	very soluble
Solubility in ethanol	slightly soluble
Solubility in methanol	very soluble
Pharmacology
Legal status	AU: S9 (Prohibited)
Vapor pressure	{{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Muscimol (also known as agarin or pantherine) is the principal psychoactive constituent of Amanita muscaria and related species of mushroom. Muscimol acts as a potent, selective agonist for the GABA_A receptors and displays sedative-hypnotic and dissociative psychoactivity.

Chemistry

Muscimol is the psychoactive compound responsible for the effects of Amanita muscaria intoxication. Ibotenic acid, a neurotoxic secondary metabolite of Amanita muscaria, serves as a prodrug to muscimol when the mushroom is ingested or dried, converting to muscimol via decarboxylation.

It can be produced synthetically from propargyl chloride. The lithium acetylide is produced by reaction with BuLi. Remaining at -40 °C this is treated with a two-fold excess of ethyl chloroformate to afford ethyl 4-chlorotetrolate. This is added to an aqueous methanolic solution of basic hydroxylamine at -35 °C followed 15 min later by a pH 7 aqueous buffer so as to give a final pH between 8.5 and 9 for optimum cyclisation. The resulting chloromethylisoxazole is heated to 50 °C in a solution of methanol saturated (at 0 °C) with anhydrous ammonia for 5 hours in a sealed flask to give muscimol. The overall yield achieved in the literature was 18.7%.

Biology

Muscimol is produced naturally in the mushrooms Amanita muscaria and Amanita pantherina, along with muscarine, muscazone, and ibotenic acid. A. muscaria and A. pantherina should be eaten with caution and prepared properly to lessen effects of nausea; no official deaths from poisoning have been recorded from A. muscaria and A. pantherina. 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

Pharmacology

Muscimol is a potent GABA_A agonist, activating the receptor for the brain's principal inhibitory neurotransmitter, GABA. Muscimol binds to the same 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. 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.

While muscimol is conventionally thought of as a selective GABA_A agonist, it is also a partial agonist at the GABA_A-rho receptor, and so its range of effects results from a combined action at both targets.

In patients with Huntington's disease and chronic schizophrenia, oral doses of muscimol have been found to cause a rise of both prolactin and growth hormone.

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

When consumed, some percentage of muscimol goes un-metabolized and thus excreted in urine, a phenomenon exploited by practitioners of the traditional entheogenic use of Amanita muscaria.

The psychoactive dose of muscimol is around 10–15 mg for a normal person. A Guide to British Psilocybin Mushrooms by Richard Cooper published in 1977 recommends a smaller dose, 8.5 mg, and suggests that it is possible for this amount to be present in as little as 1 g of dried A. muscaria but this is not consistent with most other reports which suggest 5-10g is necessary. A correct dose may be difficult to determine because potency varies dramatically from one mushroom to the next.

Toxicity

The LD₅₀ in mice is 3.8 mg/kg s.c, 2.5 mg/kg i.p. The LD₅₀ in rats is 4.5 mg/kg i.v, 45 mg/kg orally.

Effects

Many of muscimol's effects are consistent with its pharmacology as a GABA_A receptor agonist, presenting many depressant or sedative-hypnotic effects. Atypical of the effect profile of sedative drugs generally however, muscimol, like Z-drugs, can cause dissociative changes in perception. Jonathan Ott describes the effects of Amanita pantherina below:

About 90 minutes after ingestion ... I noticed that I was experiencing changes in visual perception. These effects became stronger over the next hour or some, and were characterized by sensing an 'alive quality' in inanimate objects, wavy motion in the visual field like a Van Gogh canvas ... and mild distortion of size, distance and depth perception. Auditory hallucination were also prominent -- especially the effect, called 'anahata sounds' of yoga, of hearing fine high-pitched sounds like bells and violin strings.

Legal Status

Australia

Muscimol is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.

See also

• Psychedelic drug
• Amanita muscaria
• Amanita pantherina
• Ibotenic acid
• Gaboxadol
• Thiomuscimol

References

Additional references

• Rätsch, Christian. (1998). The Encyclopedia of Psychoactive Plants. Rochester, VT: Park Street Press.

External links

• Psychoactive Amanitas on Erowid