Muscimol

Muscimol, also known as agarin, pantherine, or pyroibotenic acid, is a GABAA receptor agonist with sedative and hallucinogenic effects and the principal psychoactive constituent of Amanita mushrooms such as Amanita muscaria (fly agaric) and Amanita pantherina (panther cap). It is a 3-hydroxyisoxazole alkaloid and is closely related structurally to the neurotransmitter γ-aminobutyric acid (GABA). The compound is widely used as a ligand and agonist of the GABAA receptor in scientific research. Muscimol is typically taken orally, but may also be smoked. Peak effects occur after 1 to 3 hours orally and its duration is 4 to 10 hours but up to 24 hours. The effects of muscimol in humans include central depression, sedation, sleep, cognitive and motor impairment, hallucinations, perceptual distortion, and muscle twitching, among others. Muscimol acts as a potent GABAA receptor full agonist. However, it acts as a preferential supra-maximal agonist at extrasynaptic δ subunit-containing GABAA receptors. It is also a potent GABAA-ρ receptor partial agonist and a weak GABA reuptake inhibitor. The drug is inactive at the GABAB receptor but is a substrate of GABA transaminase (GABA-T). Muscimol mostly exerts its effects via GABAA receptor activation. It is very different from drugs like benzodiazepines and barbiturates as it is an orthosteric agonist of the GABAA receptor rather than an allosteric modulator. Unlike GABA, muscimol crosses the blood–brain barrier and hence is centrally active. Muscimol is a conformationally restrained analogue of GABA. The related compound and Amanita species constituent ibotenic acid is a prodrug of muscimol, but also has neurotoxic effects. Muscimol was first isolated from Amanita muscaria and hence was discovered in 1964. It has been limitedly clinically studied as a potential pharmaceutical drug for a number of uses, such as treatment of epilepsy. In addition, analogues and derivatives of muscimol, such as the selective GABAA receptor...