4 years ago

The Synthesis and Evaluation of Fluoro-, Trifluoromethyl-, and Iodomuscimols as GABA Agonists

The Synthesis and Evaluation of Fluoro-, Trifluoromethyl-, and Iodomuscimols as GABA Agonists
David O'Hagan, Michael Bühl, Vivian W. Y. Liao, Alexandra M. Z. Slawin, David B. Cordes, Mary Chebib, Han. C. Chua, Mohd Abdul Fatah Abdul Manan
Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C-4 fluorine-containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor. Magical Mushroom Muscimol! Muscimol is a neurotoxin and potent GABA receptor agonist from the mushroom Amanita muscaria. The first halogenated analogues (F-, I-, CF3-) of muscimol have been prepared, locating the halogen at the C-4 position. Only the mono fluoro analogue showed activity at GABA receptors, displaying a greater maximum response in comparison to GABA at the extrasynaptic GABAA receptors, but lower overall potency. Background photo by Onderwijsgekk is licensed under CC BY-SA 3.0 NL

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701443

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