Invited Speaker

Conversion of Natural Toxins such as the Mushroom Toxins Muscimol and Ibotenic Acid into Glutamate Receptor Ligands
Kristian Stromgaard
Denmark





The neurotransmitters γ-aminobutyric acid (GABA) and glutamate are the principal inhibitory and excitatory, respectively neurotransmitters in the central nervous system. Thus, GABA and glutamate are vital for the normal physiological function of the brain and are profoundly involved in a plethora of diseases in the brain. Thus a thorough understanding of these transmitter systems is of utmost importance in the unraveling of the basic functions of our brain, as well as in the potential treatment of brain diseases, such as Alzheimer’s disease and schizophrenia. Notably, constituents of the toxic mushroom Amanita muscaria have proven to be exceptionally useful in such studies.

In seminal work by Povl Krogsgaard-Larsen and colleagues, exploited muscimol and ibotenic acid from Amanita muscaria in extensive medicinal chemistry studies providing a number of both indispensable pharmacological tools as well as clinically relevant compounds. Muscimol have been used as a lead structure providing several compounds with various effects in the GABA area, most notably THIP (Gaboxadol), which is being pursued as a novel type hypnotic. Similarly, ibotenic acid has lead to a-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), which is defining a subgroup of glutamate receptors, the AMPA receptors.

These studies together with related studies on other types of neuroactive natural products, and how these have been exploited with respect to fine-tuning their pharmacological profiles at glutamate receptors will be presented in the talk.