Muscimol

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^[3] and a potent and selective orthosteric agonist for the GABA_A receptor^[4] It displays sedative–hypnotic, depressant, and hallucinogenic psychoactivity.^[5] 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. 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.^[6]