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Xiaotong Liu,홍성인,박세진,DELAPENAJUNEBRYAN,Haiyan Che,윤서영,김동현,김종민,Mudan Cai,Victoria Risbrough,Mark A. Geyer,신찬영,정재훈,박해일,류재환,류종훈 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.7
We previously reported that oroxylin A, ac-aminobutyric acid A (GABAA) receptor antagonist,ameliorates drugs-induced memory impairments. We synthesizedseveral oroxylin A derivatives in efforts to find asubstance that has pro-cognitive effects as well as improvessensorimotor gating. The aim of the present study is toinvestigate the effect of a novel oroxylin A derivative,5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on pharmacological models of schizophrenia,which exhibit memory impairment and sensorimotor gatingdeficit. Memory impairment was induced by scopolamine,a muscarinic receptor antagonist, or MK-801, an N-methyl-Daspartatereceptor antagonist. Sensorimotor gating deficitswere induced by MK-801 and measured by prepulse inhibition(PPI) of the acoustic startle response task. DMPC treatment(20 mg/kg) significantly attenuated scopolamine- or MK-801-induced memory impairment and it even enhanced cognitiveperformance of normal animals. Furthermore, DMPC significantlyameliorated MK-801-induced PPI deficits in theacoustic startle response task. In an in vitro study, DMPC(20 lM) inhibited intracellular Cl- influx induced by muscimol,a selective GABAA receptor agonist. These results suggestthat DMPC would be a potential candidate for alleviatingcognitive dysfunction and sensorimotor gating deficits inschizophrenia, and that its effects may be mediated, in part, viablockade of the GABAergic neurotransmitter system.