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ZK 200775 is a competitive GluR (AMPA)/kainate antagonist. In rat cortical membranes, it displays high affinity for [3H]-AMPA (Ki = 120 nM) and [3H]-CNQX (Ki = 32 nM) binding sites but low affinity for kainate and NMDA channel-associated binding sites (IC50 values range from 2.5 to 11 μM). It inhibits currents induced by AMPA, kainate and NMDA with IC50 values of 21 nM, 27 nM, and > 1 μM respectively. AMPA is a transmembrane glutamate receptor composed of the subunits GluR-1,2,3,4.
Turski et al (1998) ZK200775: a phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proc.Natl.Acad.Sci.USA. 95 10960. Kosowski et al (2004) Nicotine-induced dopamine release in the nucleus accumbens is inhibited by the novel AMPA antagonist ZK200775 and the NMDA antagonist CGP39551. Pychopharmacology 175 114. Elger et al (2005) Novel a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonists of 2,3-benzodiazepine type: chemical synthesis, in vitro characterization, and in vivo prevention of acute neurodegeneration. J.Med.Chem. 48 4618.
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