PEAQX is a potent orally active NMDA antagonist, with IC50 values of 0.270μM for hNMDA 1A/2A and 29.6μM for 1A/2B receptors, respectively [1]. PEAQX is widely used in animal models to regulate motor ability and brain function[2].
In vitro, PEAQX treatment (5μM) for 5min inhibited Ca2+ influx induced by NMDA in rat primary neuronal cells [3]. Treatment with 3μM PEAQX for 12h induced apoptosis and increased caspase-3 levels in corticostriatal organotypic slice cultures[4].
In vivo, A single dose of 20mg/kg subcutaneous injection of PEAQX for 30min reduced the incidence of generalized seizures (GS) in a rat model of convulsive seizures[5]. A single subcutaneous injection of 3.75mg/kg PEAQX could improve the global social activities of adolescent male Sprague-Dawley rats within 2 days[6]. Subcutaneous injection of PEAQX (10mg/kg) twice daily for 14 days resulted in neonatal rats showing spatial working memory deficits as well as enhanced responsiveness to sound stimuli[7].
References:
[1] Auberson Y P, Allgeier H, Bischoff S, et al. 5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition[J]. Bioorganic & medicinal chemistry letters, 2002, 12(7): 1099-1102.
[2] Egunlusi A O, Joubert J. NMDA receptor antagonists: emerging insights into molecular mechanisms and clinical applications in neurological disorders[J]. Pharmaceuticals, 2024, 17(5): 639.
[3] Brittain M K, Brustovetsky T, Brittain J M, et al. Ifenprodil, a NR2B-selective antagonist of NMDA receptor, inhibits reverse Na+/Ca2+ exchanger in neurons[J]. Neuropharmacology, 2012, 63(6): 974-982.
[4] Anastasio N C, Xia Y, O'Connor Z R, et al. Differential role of N-methyl-D-aspartate receptor subunits 2A and 2B in mediating phencyclidine-induced perinatal neuronal apoptosis and behavioral deficits[J]. Neuroscience, 2009, 163(4): 1181-1191.
[5] Mares P, Tsenov G, Kubova H. Anticonvulsant action of GluN2A-preferring antagonist PEAQX in developing rats[J]. Pharmaceutics, 2021, 13(3): 415.
[6] Morales M, Varlinskaya E I, Spear L P. Low doses of the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, induces social facilitation in adolescent male rats[J]. Behavioural brain research, 2013, 250: 18-22.
[7] Furuie H, Yamada M. Neonatal blockade of NR2A-containing but not NR2B-containing NMDA receptor induces spatial working memory deficits in adult rats[J]. Neuroscience Research, 2022, 176: 57-65.
PEAQX是一种强效且有口服活性的NMDA受体拮抗剂，对hNMDA 1A/2A和1A/2B受体的IC50值分别为0.270μM和29.6μM[1]。PEAQX广泛应用于动物模型中调节运动能力和脑功能[2]。
在体外，5μM的PEAQX处理大鼠原代神经元细胞5分钟可抑制NMDA诱导的Ca2+内流[3]。3μM的PEAQX处理皮质纹状体器官型脑片培养物12小时能诱导细胞凋亡并增加caspase-3水平[4]。
在体内，惊厥发作大鼠模型单次皮下注射20mg/kg剂量的PEAQX（30分钟）可降低全身性癫痫发作发生率[5]。青春期雄性Sprague-Dawley大鼠单次皮下注射3.75mg/kg剂量的PEAQX能在2天内改善整体社交活动[6]。新生大鼠每日两次皮下注射10mg/kg的PEAQX（持续14天）会导致空间工作记忆缺陷并增强对声音刺激的反应性[7]。