Product Code Database
Muscimol, also known as agarin or pantherine, as well as 5-(aminomethyl)-1,2-oxazol-3-ol, is the principal psychoactive constituent of Amanita muscaria and Amanita pantherina. Muscimol is an isoxazole alkaloid and a potent and selective agonist for the GABAA receptor It displays sedative, depressant, and psychoactivity. It is widely used to study GABAergic function in the brain.
Muscimol is under investigation for its potential to treat anxiety, insomnia, and neurological disorders, though its psychoactive nature requires careful regulation. A systematic review and meta-analysis of 22 studies found that muscimol reduces neuropathic pain symptoms, with effects beginning within 15 minutes and lasting up to three hours. Muscimol was tested in small clinical trials between 1977 and 1982 for conditions like schizophrenia, Huntington’s disease, and tardive dyskinesia, but showed limited efficacy and was eventually supplanted by the related compound gaboxadol. A later phase I trial for epilepsy in 2012 was also discontinued.
It was first isolated from Amanita pantherina in 1964, has a semi-rigid isoxazole structure and can be extracted from mushrooms or synthesized through various chemical routes, with modern methods improving upon earlier low-yield syntheses.
In vivo, muscimol exhibits dose-dependent effects with reversible central nervous system symptoms at higher doses and is rapidly metabolized in the brain without evidence of long-term toxicity. In Australia, muscimol is classified as a Schedule 9 prohibited substance, meaning its use is highly restricted and only allowed for approved scientific or medical purposes. In the United States, it is not federally controlled, but the FDA has deemed A. muscaria and muscimol unapproved for use in foods and is currently reviewing their use in dietary supplements. Louisiana banned the consumption of A. muscaria in 2005.
Muscimol is recognized as a potent agonist for ionotropic GABA-A receptors. By mimicking the inhibitory neurotransmitter GABA, muscimol activates these receptors, leading to the opening of chloride channels and subsequent hyperpolarization of neurons. This results in decreased neuronal excitability, which is crucial for maintaining the balance between excitation and inhibition in the central nervous system.
The biochemical properties of muscimol make it a valuable tool for investigating GABAergic mechanisms. Its high affinity and specificity for GABA-A receptors allow researchers to study synaptic transmission, neural circuit dynamics, and the overall role of GABAergic inhibition in various physiological and pathological states.
A study on nonhuman primates indicated that muscimol, when administered in escalating doses, caused reversible hyperkinesia and dyskinesias at higher doses (up to 88.8 mM), but no long-term toxicity was observed on histological examination.
The median lethal dose 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.
Muscimol has shown potential as an anticonvulsant, blocking seizures induced by various agents in animal models without causing significant toxicity at therapeutic doses.
Muscimol exhibits dose-dependent efficacy with higher doses leading to significant, but reversible, CNS symptoms.
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. (2025). 9780123864550 ISBN 9780123864550
When consumed, a substantial percentage of muscimol goes un-metabolized and thus excreted in urine, a phenomenon exploited by Siberian practitioners of the traditional use of Amanita muscaria."" p. 228 in: (2025). 9780195146639 ISBN 9780195146639
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.
Recent research has highlighted the following effects of muscimol:
/ref>
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.
(2) was then refluxed in concentrated hydrochloric acid to hydrolyze the methoxy group, and the zwitterion crystallized from a solution of methanol and tetrahydrofuran after the addition of triethylamine, resulting in a 50% yield. Chemists report having struggled to reproduce these results. More dependable and scalable procedures have been developed, two examples being the syntheses of McCarry and Varasi.
McCarry's synthesis is a three step synthesis involving a lithium acetylide produced from propargyl chloride. The acetylide (3), was dissolved in ether, cooled to -40 °C, and treated with excess ethyl chloroformate to afford ethyl 4-chlorotetrolate (4) in a 70% yield. (4) was then added to a solution of water, methanol and hydroxylamine at -35 °C. At a pH of between 8.5 and 9, the isoxazole (5) was recovered in a 41% yield. Muscimol was formed in a 65% yield when (5) was dissolved in a saturated solution of methanol and anhydrous ammonia and heated from 0 °C to 50 °C. The total yield was 18.7%.
Varasi's synthesis is notable for its inexpensive starting materials and mild conditions. It begins with the combination of 2,3-Dichloro-1-propene (6), potassium bicarbonate, water, and dibromoformaldoxime (7) ( which is a well known precursor of bromo nitriloxyde, a reactive dipole for regioselective Diels-Alder cycloadditions, which forms in alkali), all dissolved in ethyl acetate. 5-Chloromethyl-3-bromoisoxazole (8) was extracted with an experimental yield of 81%. 5-Aminomethyl-3-bromoisoxazole (9) was formed in 90% yield by the combination of (8) and ammonium hydroxide in dioxane.
(9) was then refluxed with potassium hydroxide in methanol to generate 5-Aminomethyl-3-methoxyisoxazole (10) with a 66% yield. Subsequent reflux of (10) with hydrobromic acid and acetic acid generated muscimol with a yield of 62%. The overall synthetic yield was 30%.
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.
|
|
