The Synthesis and Evaluation of Fluoro‐, Trifluoromethyl‐, and Iodomuscimols as GABA Agonists. Issue 45 (24th July 2017)

• Record Type: Journal Article
• Authors: Abdul Manan, Mohd Abdul Fatah; Cordes, David B.; Slawin, Alexandra M. Z.; Bühl, Michael; Liao, Vivian W. Y.; Chua, Han. C.; Chebib, Mary; O'Hagan, David
• Is Part Of: Chemistry. Volume 23:Issue 45(2017)
• Page Start: 10848
• Page End: 10852
• Publication Date: 2017-07-24
• Subjects: gaba agonists -- gaba receptors fluorination -- iodination -- muscimol -- trifluoromethyl; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201701443
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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 (α1 β2 γ2 ) and extrasynaptic (α4 β2 γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4 β2 γ) receptor. Abstract : 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