NBQX disodium salt
(Synonyms: 6-硝基-7-硫氨基苯并[F]喹喔啉-2,3二酮,FG9202 disodium) 目录号 : GC13482
An AMPA/kainate glutamate receptor antagonist
Cas No.:479347-86-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HIP-009 cells |
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Preparation Method |
Assessed the effects of NBQX disodium salt and CNQX—antagonists of AMPARs and KARs—on the AMPA- or KA-evoked calcium rise to confirm the functions of these receptors in differentiated HIP-009 cells. |
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Reaction Conditions |
30 µM NBQX disodium salt |
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Applications |
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. |
| Animal experiment [2]: | |
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Animal models |
Male Wistar rats |
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Preparation Method |
To observe anti-epileptic effects of NBQX disodium salt in PTZ induced epilepsy,rats into four groups: rats in saline + saline group were treated with saline only; rats in PTZ + saline group were treated with 50 mg/kg of PTZ and saline for 28 days; rats in saline + NBQX disodium salt group were treated with saline for 28 days, and 20 mg/kg of NBQX disodium salt for next 3 days; rats in PTZ + NBQX disodium salt group were treated with 50 mg/kg of PTZ for 28 days and were treated with 20 mg/kg of NBQX disodium salt for next 3 days. Behavioral tests and neurochemical analysis were performed on the following 2 days. |
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Dosage form |
20 mg/kg NBQX disodium salt Once daily by intraperitoneal injection for 3 days |
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Applications |
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. |
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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. | |
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]。
| Cas No. | 479347-86-9 | SDF | |
| 别名 | 6-硝基-7-硫氨基苯并[F]喹喔啉-2,3二酮,FG9202 disodium | ||
| 化学名 | sodium 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-bis(olate) | ||
| Canonical SMILES | O=S(N)(C1=CC=CC2=C1C([N+]([O-])=O)=CC(N=C3[O-])=C2N=C3[O-])=O.[Na+].[Na+] | ||
| 分子式 | C12H6N4O6SNa2 | 分子量 | 380.24 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 20 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6299 mL | 13.1496 mL | 26.2992 mL |
| 5 mM | 0.526 mL | 2.6299 mL | 5.2598 mL |
| 10 mM | 0.263 mL | 1.315 mL | 2.6299 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Synaptic pathways that shape the excitatory drive in an OFF retinal ganglion cell
J Neurophysiol2012 Apr;107(7):1795-807.PMID: 22205648DOI: 10.1152/jn.00924.2011
Different types of retinal ganglion cells represent distinct spatiotemporal filters that respond selectively to specific features in the visual input. Much about the circuitry and synaptic mechanisms that underlie such specificity remains to be determined. This study examines how N-methyl-d-aspartate (NMDA) receptor signaling combines with other excitatory and inhibitory mechanisms to shape the output of small-field OFF brisk-sustained ganglion cells (OFF-BSGCs) in the rabbit retina. We used voltage clamp to separately resolve NMDA, ¦Á-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and inhibitory inputs elicited by stimulation of the receptive field center. Three converging circuits were identified. First is a direct glutamatergic input, arising from OFF cone bipolar cells (CBCs), which is mediated by synaptic NMDA and AMPA receptors. The NMDA input was saturated at 10% contrast, whereas the AMPA input increased monotonically up to 60% contrast. We propose that NMDA inputs selectively enhance sensitivity to low contrasts. The OFF bipolar cells, mediating this direct excitatory input, express dendritic kainate (KA) receptors, which are resistant to the nonselective AMPA/KA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX), but are suppressed by a GluK1- and GluK3-selective antagonist, (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxy-thiophene-3-yl-methyl)-5-methylpyrimidine-2,4-dione (UBP-310). The second circuit entails glycinergic crossover inhibition, arising from ON-CBCs and mediated by AII amacrine cells, which modulate glutamate release from the OFF-CBC terminals. The third circuit also comprises glycinergic crossover inhibition, which is driven by the ON pathway; however, this inhibition impinges directly on the OFF-BSGCs and is mediated by an unknown glycinergic amacrine cell that expresses AMPA but not KA receptors.
Pharmacological characterization of harmaline-induced tremor activity in mice
Eur J Pharmacol2009 Aug 15;616(1-3):73-80.PMID: 19497322DOI: 10.1016/j.ejphar.2009.05.031
Harmaline-induced tremor in rodents is a model of essential tremor. We utilized a novel assay to quantify tremor activity in mice and found that tremor activity was dependent on harmaline dose. The first-line clinical essential tremor treatments propranolol, primidone and gabapentin and gamma-hydroxybutyrate (GHB) significantly attenuated harmaline-induced tremor. The anticonvulsants valproate and carbamazepine and the mood stabilizer lithium suppressed harmaline-induced tremor. The gamma-amino-butyric acid (GABA) receptor subtype A receptor agonist muscimol attenuated harmaline-induced tremor. By contrast, the GABA(B) receptor agonist R-baclofen increased tremor at the lowest dose tested, but had no effects at higher doses. Administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine or 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801) attenuated harmaline-induced tremor. The competitive NMDA antagonist D-4-[(2E)-3-phosphono-2-propenyl]-2-piperazinecarboxylic acid (d-CPPene) dose-dependently blocked harmaline-induced tremor, as did the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX). The metabotropic glutamate subtype 5 (mGlu5) receptor antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) was inactive against tremor. The dopamine reuptake inhibitor GBR12909 and the dopamine D(1)/D(2) receptor agonist apomorphine attenuated harmaline-induced tremor. Follow-up studies indicated that dopamine D(2)/D(3) but not dopamine D(1) receptor activation likely mediates the effects of apomorphine and GBR12909. Administration of compounds with sedative side-effects had no effect on tremor activity. In summary, the present data confirm the pharmacological validity of harmaline-induced tremor in mice, quantified via a novel assay, as an animal model of essential tremor. Further, these data provide additional evidence for the roles of ionotropic glutamate, GABA(A) and dopamine D(2)/D(3) receptors in the neurobiology of harmaline-induced tremor.
Roles of the spinal glutamatergic pathway activated through ¦Á-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and its interactions with spinal noradrenergic and serotonergic pathways in the rat urethral continence mechanisms
Neurourol Urodyn2015 Jun;34(5):475-81.PMID: 24668912DOI: 10.1002/nau.22588
Aims: To investigate the role of the glutamatergic pathway and its relationship to noradrenergic and serotonergic pathways in modulation of the urethral continence reflex during sneezing in rats.
Methods: In female Sprague-Dawley rats under urethane anesthesia, the effects of an ¦Á-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5-HT)]2B/2C agonist on the amplitude of urethral responses during sneezing (AURS), urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP) were investigated.
Results: Intrathecal application (i.t.) of NBQX disodium salt (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately 60% without affecting UBP and caused stress urinary incontinence (SUI) during sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake inhibitor, and mCPP (i.t.), a 5-HT(2B/2C), agonist increased AURS, and NBQX (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.), whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of NBQX (i.t.).
Conclusion: These results indicate that the glutamatergic pathway acting through AMPA receptors plays a crucial role on the active urethral closure reflex during sneezing at the spinal level, and noradrenergic and serotonergic pathways modulate the reflex via the spinal glutamatergic system in rats.
Glial GLT-1 blockade in infralimbic cortex as a new strategy to evoke rapid antidepressant-like effects in rats
Transl Psychiatry2017 Feb 21;7(2):e1038.PMID: 28221365DOI: 10.1038/tp.2017.7
Ketamine and deep brain stimulation produce rapid antidepressant effects in humans and rodents. An increased AMPA receptor (AMPA-R) signaling in medial prefrontal cortex (mPFC) has been suggested to mediate these responses. However, little research has addressed the direct effects of enhancing glutamate tone or AMPA-R stimulation in mPFC subdivisions. The current study investigates the behavioral and neurochemical consequences of glutamate transporter-1 (GLT-1) blockade or s-AMPA microinfusion in the infralimbic (IL) and prelimbic (PrL) cortex. Owing to the connectivity between the mPFC and raphe nuclei, the role of serotonin is also explored. The bilateral microinfusion of the depolarizing agent veratridine into IL -but not PrL- of rats evoked immediate antidepressant-like responses. The same regional selectivity was observed after microinfusion of dihydrokainic acid (DHK), a selective inhibitor of GLT-1, present in astrocytes. The DHK-evoked antidepressant-like responses appear to be mediated by an AMPA-R-driven enhancement of serotonergic activity, as (i) they were prevented by NBQX 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt) and mimicked by s-AMPA; (ii) DHK and s-AMPA elevated similarly extracellular glutamate in IL and PrL, although extracellular 5-HT and c-fos expression in the midbrain dorsal raphe increased only when these agents were applied in IL; and (iii) DHK antidepressant-like responses were prevented by 5-HT synthesis inhibition and mimicked by citalopram microinfusion in IL. These results indicate that an acute increase of glutamatergic neurotransmission selectively in IL triggers immediate antidepressant-like responses in rats, likely mediated by the activation of IL-raphe pathways, which then results in a fast increase of serotonergic activity.
Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei
Eur J Neurosci2007 Jul;26(1):23-32.PMID: 17596193DOI: 10.1111/j.1460-9568.2007.05645.x
In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with gamma-aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABA(A) (bicuculline), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate [2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide disodium salt (NBQX)], N-methyl-D-aspartate (NMDA) [D-(-)-2-amino-5-phosphonopentanoic acid (AP-5)] and group I metabotropic glutamate receptors (mGlu-I) [(R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABA(A) receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABA(A) inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABA(A) receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABA(A) and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal conditions and during the stress response that accompanies many forms of vestibular dysfunction.