CX546 is a selective positive AMPAR modulator; the prototypical ampakine agent. Intraperitoneal injections of CX546 increased hippocampal BDNF (brain-derived neurotrophic factor) mRNA levels in aged rats and middle-aged mice[3]. Administration of the positive modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPAR), CX546, during the conditioning phase only, improved the disrupted LI in mGluR5 knockout mice and facilitated LI in control C57BL/6J mice, given extended number of conditioning trails. PPI (Prepulse inhibition) deficit of mGluR5(-/-) mice was effectively reversed by CX546, whereas aniracetam had a less pronounced effect[4]. In binding tests, CX546 caused an approximately 2-fold increase in the affinity for radiolabeled agonists, whereas CX516 was ineffective[5]. CX546 reduced the degree of desensitization more potently than CX516 or IDRA 21, but not as efficiently as cyclothiazide. CX546 increased agonist affinity threefold on nondesensitizing AMPA receptors by slowing agonist unbinding. In the presence of CX546, the current induced by short pulses of glutamate from recombinant GluR2 receptors decayed with a time course that was approximately twentyfold faster than EPSCs[6].
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