CX 546 is a potent activator of 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, with an EC50 value of 93.2µM[1]. CX 546 greatly prolonged the duration of synaptic responses and hippocampal excitatory postsynaptic currents in animals[2]. CX 546 has been widely used as a regulator of central nervous system functions and is involved in influencing various energy metabolism pathways[3].
In vitro, CX 546 treatment at 50μM for 48 hours led to an increase in cell proliferation and enhanced viability in subventricular zone (SVZ) cells of mice[4]. CX 546 treatment at 200μM for 72 hours reversed the inhibition of viability caused by cisplatin (10μM) and reduced cell death[5].
In,vivo, CX 546 treatment (0.5mg/kg/day) via intraperitoneally administration into the infarction rat model for 4 weeks exacerbated the infarction symptoms and tissue damage, activated the TLR4/NF-κB pathway, and impaired the cardiac function[6]. A single intraperitoneal injection of CX 546 at a dose of 16mg/kg into newborn rats can effectively reverse the respiratory depression caused by opioid drugs and barbiturate drugs within 60min[7]. Intraperitoneally injecting a single dose of CX 546 (10mg/kg) into the rat model could suppress chronic neuropathic pain caused by acute noxious stimulus within 5 minutes[8].
References:
[1] Pellerin L, Magistretti P J. Ampakine™ CX546 bolsters energetic response of astrocytes: a novel target for cognitive‐enhancing drugs acting as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor modulators[J]. Journal of neurochemistry, 2005, 92(3): 668-677.
[2] Arai A C, Xia Y F, Rogers G, et al. Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action[J]. The Journal of pharmacology and experimental therapeutics, 2002, 303(3): 1075-1085.
[3] Nagarajan N, Quast C, Boxall A R, et al. Mechanism and impact of allosteric AMPA receptor modulation by the AmpakineTM CX546[J]. Neuropharmacology, 2001, 41(6): 650-663.
[4] Schitine C, Xapelli S, Agasse F, et al. Ampakine CX546 increases proliferation and neuronal differentiation in subventricular zone stem/progenitor cell cultures[J]. European Journal of Neuroscience, 2012, 35(11): 1672-1683.
[5] Lomeli N, Pearre D C, Cruz M, et al. Cisplatin induces BDNF downregulation in middle-aged female rat model while BDNF enhancement attenuates cisplatin neurotoxicity[J]. Experimental neurology, 2024, 375: 114717.
[6] Li Z, Yu Z, Cui S, et al. AMPA receptor inhibition alleviates inflammatory response and myocardial apoptosis after myocardial infarction by inhibiting TLR4/NF-κB signaling pathway[J]. International Immunopharmacology, 2024, 133: 112080.
[7] Ren J, Poon B Y, Tang Y, et al. Ampakines alleviate respiratory depression in rats[J]. American journal of respiratory and critical care medicine, 2006, 174(12): 1384-1391.
[8] Talay R S, Liu Y, Michael M, et al. Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain[J]. Progress in neurobiology, 2021, 201: 102001.
CX 546是一种强效的3-羟基-5-甲基-4-异唑丙酸（AMPA）受体激活剂，EC50值为93.2µM[1]。CX 546能显著延长动物突触响应时间及海马兴奋性突触后电流[2]。CX 546被广泛应用于中枢神经系统功能调节，并参与多种能量代谢通路的调控[3]。
在体外，50μM浓度的CX 546处理48小时可促进小鼠脑室下区（SVZ）细胞增殖并增强细胞活力[4]。200μM的CX 546处理72小时能逆转顺铂（10μM）引起的细胞活力抑制并减少细胞死亡[5]。
在体内，梗死大鼠模型经腹腔注射CX 546（0.5mg/kg/day）4周后，梗死症状和组织损伤加剧，TLR4/NF-κB通路被激活，心脏功能受损[6]。给新生大鼠腹腔注射16mg/kg 单剂量的CX 546可在60分钟内有效逆转阿片类药物和巴比妥类药物引起的呼吸抑制[7]。给大鼠模型单次腹腔注射10mg/kg剂量的CX 546能在5分钟内抑制急性伤害性刺激引发的慢性神经病理性疼痛[8]。