CX 546 是第一代选择性苯甲酰胺型正 AMPAR 调节剂。
CX546 is a selective positive AMPAR modulator; the prototypical ampakine agent.IC50 value:Target: AMPAR agonistin vitro: Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA and protein levels in cultured rat entorhinal/hippocampal slices [1]. in contrast to cyclothiazide or IDRA 21, the Ampakine CX546 binds specifically to the agonist bound nondesensitized receptor, most likely acting by destabilizing the desensitized receptor conformation [2]. In binding tests, CX546 caused an approximately 2-fold increase in the affinity for radiolabeled agonists, whereas CX516 was ineffective [3]. in vivo: Intraperitoneal injections of CX546 increased hippocampal BDNF mRNA levels in aged rats and middle-aged mice [1]. 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 (four conditioning stimulus-unconditioned stimulus) [4].
参考文献:
[1]. Lauterborn JC, et al. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci. 2000 Jan 1;20(1):8-21.
[2]. Nagarajan N, et al. Mechanism and impact of allosteric AMPA receptor modulation by the ampakine CX546. Neuropharmacology. 2001 Nov;41(6):650-63.
[3]. Arai AC, et al. Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action. J Pharmacol Exp Ther. 2002 Dec;303(3):1075-85.
[4]. Lipina T, et al. The ampakine CX546 restores the prepulse inhibition and latent inhibition deficits in mGluR5-deficient mice. Neuropsychopharmacology. 2007 Apr;32(4):745-56.
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