DQP 1105 is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor, which inhibits GluN2C- and GluN2D-containing receptors with IC50 values of 7.0 and 2.7µM [1]. DQP 1105 can reversibly weaken the membrane potential and circadian rhythm of clock gene expression in suprachiasmatic nucleus (SCN) neurons by inhibiting NMDAR2C[2]. DQP 1105 has been widely used for regulating neuronal synaptic responses[3].
In vitro, DQP 1105 treatment (20µM) for 24 hours significantly reduced the levels of Cx43 protein and VIP protein in astrocytes, as well as the level of Clock mRNA[4]. 15µM DQP 1105 treatment for 10 days significantly promoted the growth of pyramidal cells and increased the number of apical dendritic branches of these cells[5]. Treatment with 10µM DQP 1105 for 4 hours can reduce the expression of p-PI3K and p-Akt in CTX-TNA2 cells treated with lipopolysaccharide (LPS) [6].
In vivo, DQP 1105 treatment via a single intraperitoneal injection at a dose of 90mg/kg impaired the motor coordination ability of CD-1 mice within 30 minutes[7]. A single intraperitoneal injection of 28mg/kg dose of DQP 1105 reduced the frequency of epileptic seizures in mice within 2 hours[8].
References:
[1] Acker T M, Yuan H, Hansen K B, et al. Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators[J]. Molecular pharmacology, 2011, 80(5): 782-795.
[2] Brancaccio M, Edwards M D, Patton A P, et al. Cell-autonomous clock of astrocytes drives circadian behavior in mammals[J]. Science, 2019, 363(6423): 187-192.
[3] Mahmoud H, Martin N, Hildebrand M E. Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development[J]. Molecular brain, 2020, 13(1): 31.
[4] Xue H, Wu M, Wang Y, et al. The circadian rhythms regulated by Cx43-signaling in the pathogenesis of Neuromyelitis Optica[J]. Frontiers in Immunology, 2023, 13: 1021703.
[5] Köhler I, Rennau L M, Hoffmann L, et al. Activation of GluN2D-containing NMDA receptors promotes development of axons and axon-carrying dendrites of cortical interneurons[J]. Cerebral Cortex, 2025, 35(6): bhaf136.
[6] Gao R, Ali T, Liu Z, et al. NMDAR (2C) deletion in astrocytes relieved LPS-induced neuroinflammation and depression[J]. International Immunopharmacology, 2024, 132: 111964.
[7] Pálfi E, Lévay G, Czurkó A, et al. Acute blockade of NR2C/D subunit‐containing N‐methyl‐D‐aspartate receptors modifies sleep and neural oscillations in mice[J]. Journal of Sleep Research, 2021, 30(4): e13257.
[8] Lozovaya N, Gataullina S, Tsintsadze T, et al. Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model[J]. Nature communications, 2014, 5(1): 4563.
DQP 1105是一种N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂，可抑制含GluN2C和GluN2D亚基受体，IC50值分别为7.0µM和2.7µM[1]。DQP 1105能够通过抑制NMDAR2C而使视交叉上核（SCN）神经元的膜电位和节律基因表达发生可逆性的减弱[2]。DQP 1105已被广泛用于调节神经元突触反应[3]。
在体外，使用20µM的DQP 1105处理星形胶质细胞24小时，显著降低了Cx43蛋白和VIP蛋白的水平，以及Clock mRNA的水平[4]。使用15µM的DQP 1105处理10天，显著促进了锥体细胞的生长，并增加了细胞的顶端树突分支数量[5]。使用10µM的DQP 1105处理经脂多糖（LPS）处理的CTX-TNA2细胞4小时，可降低p-PI3K和p-Akt的表达[6]。
在体内，单次腹腔注射90mg/kg剂量的DQP 1105，在30分钟内损害了CD-1小鼠的运动协调能力[7]。单次腹腔注射28mg/kg剂量的DQP 1105，在2小时内降低了小鼠癫痫发作的频率[8]。