0000000000321289

AUTHOR

Koichi Tsubone

showing 2 related works from this author

Pharmacological activity of C10-substituted analogs of the high-affinity kainate receptor agonist dysiherbaine

2010

Kainate receptor antagonists have potential as therapeutic agents in a number of neuropathologies. Synthetic modification of the convulsant marine toxin neodysiherbaine A (NDH) previously yielded molecules with a diverse set of pharmacological actions on kainate receptors. Here we characterize three new synthetic analogs of NDH that contain substituents at the C10 position in the pyran ring of the marine toxin. The analogs exhibited high-affinity binding to the GluK1 (GluR5) subunit and lower affinity binding to GluK2 (GluR6) and GluK3 (GluR7) subunits in radioligand displacement assays with recombinant kainate and AMPA receptors. As well, the natural toxin NDH exhibited ∼100-fold selectivi…

farmakologiakainate receptorglutamate receptorglutamaattireseptorikainaattireseptorimolekyylidynamiikkaa
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Pharmacological activity of C10-substituted analogs of the high-affinity kainate receptor agonist dysiherbaine

2009

Kainate receptor antagonists have potential as therapeutic agents in a number of neuropathologies. Synthetic modification of the convulsant marine toxin neodysiherbaine A (NDH) previously yielded molecules with a diverse set of pharmacological actions on kainate receptors. Here we characterize three new synthetic analogs of NDH that contain substituents at the C10 position in the pyran ring of the marine toxin. The analogs exhibited high-affinity binding to the GluK1 (GluR5) subunit and lower affinity binding to GluK2 (GluR6) and GluK3 (GluR7) subunits in radioligand displacement assays with recombinant kainate and AMPA receptors. As well, the natural toxin NDH exhibited approximately 100-f…

Models MolecularAgonistKainic acidPatch-Clamp TechniquesTime FactorsStereochemistrymedicine.drug_classProtein subunitGreen Fluorescent ProteinsGlutamic AcidKainate receptorAMPA receptorMolecular Dynamics SimulationLigandsTransfectionTritiumBinding CompetitiveArticleMembrane PotentialsRadioligand AssayStructure-Activity RelationshipCellular and Molecular Neurosciencechemistry.chemical_compoundReceptors Kainic AcidExcitatory Amino Acid AgonistsmedicineRadioligandHumansReceptoralpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidCell Line TransformedPharmacologyAlanineKainic AcidDose-Response Relationship DrugMolecular StructureChemistryBridged Bicyclo Compounds HeterocyclicProtein SubunitsBiochemistryMutagenesis Site-DirectedMarine toxinNeuropharmacology
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