{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T09:37:41Z","timestamp":1776505061780,"version":"3.51.2"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,1,25]],"date-time":"2012-01-25T00:00:00Z","timestamp":1327449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>Flavonoids are known to have anxiolytic and sedative effects mediated via actions on ionotropic GABA receptors. We sought to investigate this further.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>We evaluated the effects of 2\u2032\u2010methoxy\u20106\u2010methylflavone (2\u2032MeO6MF) on native GABA<jats:sub>A<\/jats:sub>receptors in new\u2010born rat hippocampal neurons and determined specificity from 18 human recombinant GABA<jats:sub>A<\/jats:sub>receptor subtypes expressed in<jats:italic>Xenopus<\/jats:italic>oocytes. We used ligand binding, two\u2010electrode voltage clamp and patch clamp studies together with behavioural studies.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>2\u2032MeO6MF potentiated GABA at \u03b12\u03b21\u03b32L and all \u03b11\u2010containing GABA<jats:sub>A<\/jats:sub>receptor subtypes. At \u03b12\u03b22\/3\u03b32L GABA<jats:sub>A<\/jats:sub>receptors, however, 2\u2032MeO6MF directly activated the receptors without potentiating GABA. This activation was attenuated by bicuculline and gabazine but not flumazenil indicating a novel site. Mutation studies showed position 265 in the \u03b21\/2 subunit was key to whether 2\u2032MeO6MF was an activator or a potentiator. In hippocampal neurons, 2\u2032MeO6MF directly activated single\u2010channel currents that showed the hallmarks of GABA<jats:sub>A<\/jats:sub>Cl<jats:sup>\u2010<\/jats:sup>currents. In the continued presence of 2\u2032MeO6MF the single\u2010channel conductance increased and these high conductance channels were disrupted by the \u03b32(381\u2013403) MA peptide, indicating that such currents are mediated by \u03b12\/\u03b32\u2010containing GABA<jats:sub>A<\/jats:sub>receptors. In mice, 2\u2032MeO6MF (1\u2013100\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>; i.p.) displayed anxiolytic\u2010like effects in two unconditioned models of anxiety: the elevated plus maze and light\/dark tests. 2\u2032MeO6MF induced sedative effects at higher doses in the holeboard, actimeter and barbiturate\u2010induced sleep time tests. No myorelaxant effects were observed in the horizontal wire test.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>2\u2032MeO6MF will serve as a tool to study the complex nature of the activation and modulation of GABA<jats:sub>A<\/jats:sub>receptor subtypes.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01604.x","type":"journal-article","created":{"date-parts":[[2011,7,28]],"date-time":"2011-07-28T11:13:26Z","timestamp":1311851606000},"page":"880-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["2\u2032\u2010Methoxy\u20106\u2010methylflavone: a novel anxiolytic and sedative with subtype selective activating and modulating actions at 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