NBQX disodium salt is a potent, highly selective and competitive antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs). Inhibition of AMPARs with NBQX disodium salt shows neuroprotective and anticonvulsant activity.
In HIP-009 cells, NBQX disodium salt inhibited both AMPA or kainic acid (KA) induced signals in a concentration-dependent manner, with IC50 values being 0.7 ± 0.1 and 0.7 ± 0.03 μM, respectively. The AMPA-evoked calcium rise was completely inhibited by NBQX disodium salt, whereas 68.6% ± 1.3% inhibition of the KA-induced signal was observed with 30 μM of NBQX disodium salt treatment[1].
NBQX disodium salt had an effect on acute seizure development, resulting in a significantly higher number of mice experiencing seizures, an increase in the number of seizures per mouse, a greater cumulative seizure score per mouse and a significantly higher mortality rate among the mice[6]. NBQX disodium salt was sufficient to decrease pentylenetetrazole-induced seizures through increasing the latency to seizures, decrease the duration of seizure onset, and reduce the scores for the severity of seizures[2]. SRS develop after status epilepticus (SE) induced by intrahippocampal injection of kainate. they were markedly suppressed by NBQX disodium salt and perampanel. However, perampanel was less tolerable than NBQX disodium salt in epileptic mice[3]. In Male Wistar rats,Although NBQX disodium salt did not affect nicotine maintenance, it significantly suppressed the drug-paired responding in the relapse session[4]. Adult male Wistar rats were trained in drinking in dark paradigm (3 weeks), and following stable alcohol intake, ketamine, NBQX disodium salt as well as their combination were injected prior to a 90 min drinking session Both doses of ketamine (5 and 10 mg/kg) and NBQX disodium salt (5 and 10 mg/kg) significantly attenuated percent alcohol intake[5]. In mice lacking NCAM and PSA, NBQX disodium salt-induced ataxia proved to be more intense as compared with wild-type mice. On both mutant backgrounds, NBQX disodium salt significantly elevated seizure thresholds during i.v. infusion of the chemoconvulsant pentylenetetrazole[7].
References:
[1]: Fukushima K, Tabata Y, et,al. Characterization of Human Hippocampal Neural Stem/Progenitor Cells and Their Application to Physiologically Relevant Assays for Multiple Ionotropic Glutamate Receptors. J Biomol Screen. 2014 Sep;19(8):1174-84. doi: 10.1177/1087057114541149. Epub 2014 Jun 30. PMID: 24980597.
[2]: Chen W, Li YS, et,al. AMPA Receptor Antagonist NBQX Decreased Seizures by Normalization of Perineuronal Nets. PLoS One. 2016 Nov 23;11(11):e0166672. doi: 10.1371/journal.pone.0166672. PMID: 27880801; PMCID: PMC5120819.
[3]: Twele F, Bankstahl M, et,al.he AMPA receptor antagonist NBQX exerts anti-seizure but not antiepileptogenic effects in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy. Neuropharmacology. 2015 Aug;95:234-42. doi: 10.1016/j.neuropharm.2015.03.014. Epub 2015 Mar 31. PMID: 25839899.
[4]: Ruda-Kucerova J, Amchova P, et,al. NBQX attenuates relapse of nicotine seeking but not nicotine and methamphetamine self-administration in rats. World J Biol Psychiatry. 2021 Dec;22(10):733-743. doi: 10.1080/15622975.2021.1907714. Epub 2021 Apr 13. PMID: 33787469.
[5]: Ruda-Kucerova J, Babinska Z, et,al.Both ketamine and NBQX attenuate alcohol drinking in male Wistar rats. Neurosci Lett. 2018 Feb 14;666:175-180. doi: 10.1016/j.neulet.2017.12.055. Epub 2017 Dec 28. PMID: 29288725; PMCID: PMC5805612.
[6]: Libbey JE, Hanak TJ, et,al. NBQX, a highly selective competitive antagonist of AMPA and KA ionotropic glutamate receptors, increases seizures and mortality following picornavirus infection. Exp Neurol. 2016 Jun;280:89-96. doi: 10.1016/j.expneurol.2016.04.010. Epub 2016 Apr 9. PMID: 27072529; PMCID: PMC4860063.
[7]: Potschka H, Pekcec A, et,al. Deficiency of neural cell adhesion molecule or its polysialylation modulates pharmacological effects of the AMPA receptor antagonist NBQX. Neuroscience. 2008 Apr 9;152(4):1093-8. doi: 10.1016/j.neuroscience.2007.09.027. Epub 2007 Sep 20. PMID: 18329813.
NBQX 二钠盐是 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) 受体 (AMPAR) 的强效、高选择性和竞争性拮抗剂。 NBQX 二钠盐对 AMPAR 的抑制作用显示出神经保护和抗惊厥活性。
在 HIP-009 细胞中,NBQX 二钠盐以浓度依赖性方式抑制 AMPA 或红藻氨酸 (KA) 诱导的信号,IC50 值分别为 0.7 ± 0.1 和 0.7 ± 0.03 μM。 AMPA 诱发的钙升高被 NBQX 二钠盐完全抑制,而 30 μM NBQX 二钠盐处理[1]观察到 KA 诱导信号的抑制率为 68.6% ± 1.3%。 p>\n
NBQX 二钠盐对急性癫痫发作有影响,导致出现癫痫发作的小鼠数量显着增加,每只小鼠的癫痫发作次数增加,每只小鼠的累积癫痫发作评分更高,死亡率显着更高小鼠[6]。 NBQX 二钠盐足以通过增加癫痫发作的潜伏期来减少戊四唑诱发的癫痫发作,减少癫痫发作的持续时间,并降低癫痫发作严重程度的评分[2]。 SRS 在海马内注射红藻氨酸诱导的癫痫持续状态 (SE) 后发展。它们被 NBQX 二钠盐和吡仑帕奈显着抑制。然而,吡仑帕奈在癫痫小鼠中的耐受性低于 NBQX 二钠盐[3]。在雄性 Wistar 大鼠中,虽然 NBQX 二钠盐不影响尼古丁维持,但它显着抑制了复发期的药物配对反应[4]。对成年雄性 Wistar 大鼠进行黑暗范式饮酒训练（3 周）,并在酒精摄入量稳定后,在 90 分钟饮酒期之前注射氯胺酮、NBQX 二钠盐及其组合两种剂量的氯胺酮（5 和 10 mg /kg) 和 NBQX 二钠盐（5 和 10 mg/kg）显着降低酒精摄入百分比[5]。在缺乏 NCAM 和 PSA 的小鼠中,与野生型小鼠相比,NBQX 二钠盐诱导的共济失调更为严重。在两种突变体背景下,NBQX 二钠盐在静脉注射期间显着提高癫痫发作阈值。输注化学惊厥剂戊四唑[7]。
NBQX 二钠盐对急性癫痫发作有影响,导致出现癫痫发作的小鼠数量显着增加,每只小鼠的癫痫发作次数增加,每只小鼠的累积癫痫发作评分更高,死亡率显着更高小鼠[6]。 NBQX 二钠盐足以通过增加癫痫发作的潜伏期来减少戊四唑诱发的癫痫发作,减少癫痫发作的持续时间,并降低癫痫发作严重程度的评分[2]。 SRS 在海马内注射红藻氨酸诱导的癫痫持续状态 (SE) 后发展。它们被 NBQX 二钠盐和吡仑帕奈显着抑制。然而,吡仑帕奈在癫痫小鼠中的耐受性低于 NBQX 二钠盐[3]。在雄性 Wistar 大鼠中,虽然 NBQX 二钠盐不影响尼古丁维持,但它显着抑制了复发期的药物配对反应[4]。对成年雄性 Wistar 大鼠进行黑暗范式饮酒训练（3 周）,并在酒精摄入量稳定后,在 90 分钟饮酒期之前注射氯胺酮、NBQX 二钠盐及其组合两种剂量的氯胺酮（5 和 10 mg /kg) 和 NBQX 二钠盐（5 和 10 mg/kg）显着降低酒精摄入百分比[5]。在缺乏 NCAM 和 PSA 的小鼠中,与野生型小鼠相比,NBQX 二钠盐诱导的共济失调更为严重。在两种突变体背景下,NBQX 二钠盐在静脉注射期间显着提高癫痫发作阈值。输注化学惊厥剂戊四唑[7]。