Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 491, Issue 1, Pages 1-8Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2004.03.014
Keywords
GABA; 6-methylflavone; benzodiazepine; flavonoid; GABA(A) receptor
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In view of the ability of flavones to displace radiolabelled benzodiazepines from brain tissue and the interesting behavioural profile of these compounds, the present study investigated the activity of 6-methylflavone at ionotropic gamma-aminobutyric acid (GABA) receptors expressed in Xenopus laevis oocytes. 6-Methylflavone (1-100 muM) was found to be a positive allosteric modulator at alpha(1)beta(2)gamma(21) and alpha(1)beta(2) GABA(A) receptors with no significant difference between the enhancement seen at either receptor subtype. At 100 muM, 6-methylflavone enhanced the response to 5 muM GABA by 183+/-20% at alpha(1)beta(2)gamma(21) .GABA(A) receptors. The methyl substiment was important since the parent flavone was significantly weaker as a positive modulator (103+/-24% enhancement of 5 muM GABA by 100 muM flavone). This enhancement is not mediated via high-affinity benzodiazepine sites as it was not inhibited by the classical benzodiazepine antagonist flumazenil under conditions where flumazenil inhibits the potentiation of the GABA response to diazepam. 6-Methylflavone (60 muM) did not significantly affect the GABA dose-response curve at rho(1) GABA(c) receptors. 6-Methylflavone acts as a positive modulator of recombinant GABA(A) receptors at sites independent of flumazenil-sensitive benzodiazepine sites. (C) 2004 Elsevier B.V. All rights reserved.
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