title: The ameliorating effects of 5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one, an oroxylin A derivative, against memory impairment and sensorimotor gating deficit in mice.
abstract: We previously reported that oroxylin A, a γ-aminobutyric acid A (GABAA) receptor antagonist, ameliorates drugs-induced memory impairments. We synthesized several oroxylin A derivatives in efforts to find a substance that has pro-cognitive effects as well as improves sensorimotor gating. The aim of the present study is to investigate 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 gating deficit. Memory impairment was induced by scopolamine, a muscarinic receptor antagonist, or MK-801, an N-methyl-D-aspartate receptor antagonist. Sensorimotor gating deficits were 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 cognitive performance of normal animals. Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the acoustic startle response task. In an in vitro study, DMPC (20 μM) inhibited intracellular Cl(-) influx induced by muscimol, a selective GABAA receptor agonist. These results suggest that DMPC would be a potential candidate for alleviating cognitive dysfunction and sensorimotor gating deficits in schizophrenia, and that its effects may be mediated, in part, via blockade of the GABAergic neurotransmitter system.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Liu
authors.forename: Sung In
authors.initials: SI
authors.lastname: Hong
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: June Bryan
authors.initials: JB
authors.lastname: Dela Peña
authors.forename: Haiyan
authors.initials: H
authors.lastname: Che
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Mudan
authors.initials: M
authors.lastname: Cai
authors.forename: Victoria
authors.initials: V
authors.lastname: Risbrough
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.forename: Haeil
authors.initials: H
authors.lastname: Park
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Lew
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000201:enzymology / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D008813:Mice, Inbred ICR; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D005419:Flavonoids; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D016660:NAD(P)H Dehydrogenase (Quinone)