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

  title={Structural features of muscimol, a potent GABAA receptor agonist, crystal structure and quantum chemicalab initio calculations},
  author={Lotte Brehm and Karla Frydenvang and Lene Hansen and Per-Ola Norrby and Povl Krogsgaard‐Larsen and Tommy Liljefors},
  journal={Structural Chemistry},
Muscimol, a constituent of the mushroomAmanita muscaria, is a semirigid analogue of the inhibitory neurotransmitter 4-aminobutyric acid (GABA). X-ray structure determinations and quantum chemicalab initio calculations (HF/6-31G*) 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 structurein vacuo. A comparison of the calculated and… 
9 Citations
DFT and Ab Initio Computational Study on the Reactivity Sites of the GABA and its Agonists, Such as CACA, TACA, DABA, and Muscimol: In the Gas Phase and Dielectric Media
The reactive behavior of GABA and its agonist molecules have been investigated using B3LYP hybrid density functional method at the 6-311++G** basis set level, in the gas phase and dielectric media.
Characterization of the GABAA Receptor Recognition Site Through Ligand Design and Pharmacophore Modeling
The existence of several modulatory sites for a number of therapeutic agents, including benzodiazepines, barbiturates, neurosteroids, and volatile anaesthetics adds to the complexity of the GABAA receptor system.
What is the form of muscimol from fly agaric mushroom (Amanita muscaria) in water? An insight from NMR experiment supported by molecular modeling
The obtained experimental spectra, supported by theoretical calculations, favor the zwitterion form of muscimol in water, which differs from NH isomer, previously determined in dimethyl sulfoxide (DMSO) solution.
Theoretical and experimental NMR studies on muscimol from fly agaric mushroom (Amanita muscaria).
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    Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
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Resolution, configurational assignment, and enantiopharmacology of 2-amino-3-[3-hydroxy-5-(2-methyl-2H- tetrazol-5-yl)isoxazol-4-yl]propionic acid, a potent GluR3- and GluR4-preferring AMPA receptor agonist.
It is concluded that (S)-2-Me-Tet-AMPA is a subunit-selective and highly potent AMPA receptor agonist and a potentially useful tool for studies of physiological AMPAceptor subtypes.
GABA and Glutamate Receptor Ligands and their Therapeutic Potential in CNS Disorders
Functionality of GABA and glutamate receptor ligands are discussed, including their therapeutic potentials in CNS disorders, including reversal of Glu transporters.


Conformational analysis of muscimol, a GABA agonist.
3- and 5-Isoxazolol zwitterions: A model of interaction with the GABA-A receptor relating to agonism and antagonism
Using molecular orbital methods, various models of interactions between GABA or analogs (TACA, muscimol, isomuscimol) and an hypothetical receptor molecular fragment, a methylguanidinium ion are proposed and results show a decrease of the interaction energy.
GABA Agonists and Uptake Inhibitors of Restricted Conformations: Structure-Activity Relations
The central γ-aminobutyric acid (GABA) system seems to be involved in the development of certain neurological and psychiatric disorders like Huntington’s chorea (McGeer and McGeer, 1976; Enna et al.,
A new class of GABA agonist
The action of these compounds as GABA agonists provides indirect evidence that GABA interacts with bicuculline-sensitive postsynaptic receptors in the cat spinal cord in a partially extended and almost planar conformation.
Reaction of Muscimol with 4‐Aminobutyrate Aminotransferase
The rate of spectral change observed on addition of muscimol to ornithine transaminase was extremely slow—at least an order of magnitude slower than that seen with GABA‐T.
A series of heterocyclic GABA analogues related to muscimol were tested as depressants of the firing of GABA sensitive neurones on the cat spinal cord, and as inhibitors of the sodium‐independent binding of GABA to rat brain membranes.
GABA agonists. Resolution, absolute stereochemistry, and enantioselectivity of (S)-(+)- and (R)-(-)-dihydromuscimol.
Compounds 4 and 5 can be considered semirigid isosteres of the conformationally flexible GABA analogues (S)-(+)- and (R)-(-)-GABOB, respectively, which show a very low degree of enantioselectivity with respect to GABA synaptic mechanisms.