Structural features of muscimol, a potent GABAA receptor agonist, crystal structure and quantum chemicalab initio calculations

Abstract

Muscimol, a constituent of the mushroom Amanita muscaria, is a semirigid analogue of the inhibitory neurotransmitter 4-aminobutyric acid (GABA). X-ray structure determinations and quantum chemical ab initio calculations (HF/6-3 IG*) have been carried out on the muscimol zwitterion. The solid-state conformations of the muscimol zwitterion are calculated to be 1.6-2.2 kcal/ mol higher in energy than that of the calculated minimum energy structure in vacuo. A comparison of the calculated and experimental structures indicates that the hydrogen bonding network in the solid state significantly affects the geometry of the molecular structure. This conclusion is supported by results of ab initio calculations on binary complexes between muscimol and an ammonium ion and between muscimol and a methoxide anion, simulating observed hydrogen bonding in the crystal structures.

Exploring ligand recognition and ion flow in comparative models of the human GABA type A receptor

“…The Cambridge Structural Database was consulted for coordinates for muscimol (CSD code: MUSIMO01) [10], flunitrazepam (CSD code: CAGWUC) [15] and alprazolam (CSD code: CIZQAD01) [72]. The coordinates of halothane were generated ab initio and its geometry optimised according to the potential of Scharf and Laasonen [77].…”

What is the form of muscimol from fly agaric mushroom (Amanita muscaria) in water? An insight from NMR experiment supported by molecular modeling

“…Its crystal structure proves the presence of a zwitterion form (a) of muscimol in the solid state. This structure was also supported by low level ab initio calculations .…”

GABAand Glutamate Receptor Ligands and their Therapeutic Potential inCNSDisorders

“…For instance, it has been shown that replacement of the 3-isoxazolol ring in these molecules by an isothiazolol ring (e.g., compound 25) has significantly different effects on the receptor affinity [72,83,109]. Furthermore, high-level quantum chemical ab initio calculations indicate that the assumed THIP-like bioactive conformation of muscimol has a very high conformational energy [110], which is not compatible with its high affinity. Furthermore, high-level quantum chemical ab initio calculations indicate that the assumed THIP-like bioactive conformation of muscimol has a very high conformational energy [110], which is not compatible with its high affinity.…”