Psychoactive Isoxazoles, Muscimol, and Isoxazole Derivatives from the Amanita (Agaricomycetes) Species: Review of New Trends in Synthesis, Dosage, and Biological Properties.

The Amanita muscaria mushroom contains alkaloids such as muscazone, muscarine, ibotenic acid, and muscimol, with the latter two acting as potent GABA agonists. Muscimol has served as a template for designing GABA agonists that do not affect GABA transaminase or GABA uptake. Analogs like THIP, THPO, iso-THIP, iso-THAZ, and 4-PIOL interact with GABA receptors differently. Conflicting opinions on the neuroprotective role of muscimol analogs against neurodegenerative diseases and their potential in treating cerebral ischemia and other health conditions motivate this review.

Study at a glance

Abstract

Herbal products found in nature can serve as great systems of study for drug design. The Amanita muscaria mushroom is native to many parts of the Northern Hemisphere and has a very distinctive appearance with its red cap and white spotted warts. The mushroom comprises several pharmacologically active alkaloids, including muscazone, muscarine, ibotenic acid, and muscimol, the latter two compounds being potent GABA agonists. Muscimol has served as a backbone in the design of GABA agonists devoid of effects on the GABA-metabolizing enzyme, GABA transaminase, and GABA uptake systems. In this sense, several analogs of muscimol have been synthesized and studied including THIP, THPO, iso-THIP, iso-THAZ and 4-PIOL which all interact with the GABA receptors much differently. The growing pharmacological and toxicological interest based on many conflicting opinions on the use of the neuroprotective role of muscimol analogs against some neurodegenerative diseases, its potent role in the treatment of cerebral ischemia and other socially significant health conditions provided the basis for this review.