Muscimol

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%.