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J. Pharmacol."},{"key":"10.1016\/j.ejmech.2019.03.043_bib187","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2004.03.014","article-title":"Flumazenil-independent positive modulation of \u03b3-aminobutyric acid action by 6-methylflavone at human recombinant \u03b11\u03b22\u03b32L and \u03b11\u03b22 GABAA receptors","volume":"491","author":"Hall","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2019.03.043_bib188","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ejphar.2005.02.034","article-title":"6-Methylflavanone, a more efficacious positive allosteric modulator of \u03b3-aminobutyric acid (GABA) action at human recombinant \u03b12\u03b22\u03b32L than at \u03b11\u03b22\u03b32L and \u03b11\u03b22 GABAA receptors expressed in Xenopus oocytes","volume":"512","author":"Hall","year":"2005","journal-title":"Eur. J. 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