Мусцимол: Әсері, қасиеттері және қолданылуы

Chemical compound

Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of Amanita muscaria and related species of mushroom. Muscimol is a potent and selective orthosteric agonist for the GABAA receptor and displays sedative hypnotic, depressant and hallucinogenic psychoactivity. This colorless or white solid is classified as an isoxazole. Muscimol went under clinical trial phase I for epilepsy, but the trial was discontinued. Muscimol, an agonist for the GABAA receptor, was able to significantly alleviate pain in its peak effect, recent studies from 2023 show. It has since been federally banned in Australia and is pending FDA review in the United States, but scientists believe it may relieve pain as well as some opioids without much of the risk of addiction associated with opioids.

Muscimol is one of the psychoactive compounds 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. Muscimol is produced in the mushrooms Amanita muscaria (fly agaric) and Amanita pantherina, along with muscarine (which is present in trace amounts and it is not active), muscazone, and ibotenic acid. A. muscaria and A. pantherina should be eaten with caution and prepared properly to lessen effects of nausea. 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.

[[File:Muscimol vs GABA 3D. png|left|thumb|GABA and muscimol molecules can have similar 3D conformations which are shown superimposed in this image. Because of this similarity, muscimol binds to certain GABA receptors. 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. While muscimol is normally thought of as a selective GABAA agonist with exceptionally high affinity to GABAA delta receptors,

Scientific studies have shown that dosing of the active ingredient muscimol is usually not precise as it has to be extracted from dried amanita mushroom. However, a psychoactive dose of muscimol is reported to be between 8 and 15 mg. As little as a gram of dried Amanita muscaria button may contain this amount of muscimol; however, the potency varies greatly among mushrooms. When consumed, a substantial percentage of muscimol goes un metabolized and thus excreted in urine, a phenomenon exploited by Siberian practitioners of the traditional entheogenic use of Amanita muscaria. 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 via IV), the EEG will show characteristic spikes.

These include euphoria, dream like (lucid) state of mind, out of body experiences and synesthesia. Negative effects include mild to moderate nausea, stomach discomfort, increased salivation and muscle twitching or tremors. In large doses strong dissociation or delirium may be felt. Many of muscimol's effects are consistent with its pharmacology as a GABAA 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 hallucinogenic changes in perception. The hallucinogenic effect produced by muscimol is most closely comparable to the hallucinogenic/Lilliputian side effects produced by some other GABAergic drugs such as zolpidem.

Muscimol was first isolated from Amanita pantherina by Onda in 1964, and thought to be an amino acid or peptide. Structure was then elucidated by Takemoto, Eugster, and Bowden. Muscimol is a semi rigid isoxazole containing both alcohol and aminomethyl substituents. Muscimol is commonly portrayed as a tautomer, where it adopts an amide like configuration. It is also commonly shown as a zwitterion.

Muscimol can be extracted from the flesh of the Amanita muscaria by treatment with boiling water, followed by rapid cooling, and further treatment with a basic resin. This is washed with water, and eluted with acetic acid using column chromatography. The eluate is freeze dried, dissolved in water, and passed down a column of cellulose phosphate. A subsequent elution with ammonium hydroxide and recrystallization from alcohol results in pure muscimol. In instances where pure muscimol is not required, such as recreational or spiritual use, a crude extract is often prepared by simmering dried Amanita muscaria in water for thirty minutes.

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."

Neither Amanita muscaria nor muscimol is considered a controlled substance by the Federal government of the United States. This means that cultivation, possession, and distribution are unregulated by the United States Federal Government. The legality of Amanita muscaria and muscimol as ingredients in food is unclear since neither are approved as food additives by the FDA. However, agriculture regulators in Florida actioned against one seller of Amanita products after the agency had determined such products were considered adulterated under state law. Muscimol may be regulated on a state level. Louisiana State Act 159 banned the possession and cultivation of the Amanita muscaria except for ornamental or aesthetic purposes. Except as a constituent of lawfully manufactured food or dietary supplements, the act outlaws preparations of the Amanita muscaria intended for human consumption, including muscimol.