NS-102
目录号 : GC64133
NS-102 是一种选择性红藻氨酸 (GluK2) 受体拮抗剂。NS-102 是一种有效的 GluR6/7 受体拮抗剂。
Cas No.:136623-01-3
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
NS-102 is a selective kainate (GluK2) receptor antagonist. NS-102 is a potent GluR6/7 receptor antagonist[1][2][3].
Combination of NS-102 (10 μM) and GYKI 52466 (30 μM) preventes full loss of compound action potentials (CAPs) during oxygen and glucose deprivation (OGD) and increases CAP area recovery[1].
NS-102 (20, 40 or 80 μmol/litre ; in the hippocampal CA3 region) significantly reduces Sevoflurane-induced hyperactivities[1].
[1]. Selva Baltan TekkÖk, et al. Excitotoxic mechanisms of ischemic injury in myelinated white matter. J Cereb Blood Flow Metab. 2007 Sep;27(9):1540-52.
[2]. P Liang, et al. Sevoflurane activates hippocampal CA3 kainate receptors (Gluk2) to induce hyperactivity during induction and recovery in a mouse model. Br J Anaesth. 2017 Nov 1;119(5):1047-1054.
[3]. Barbara Gisabella, et al. Kainate receptor-mediated modulation of hippocampal fast spiking interneurons in a rat model of schizophrenia. PLoS One. 2012;7(3):e32483.
| Cas No. | 136623-01-3 | SDF | Download SDF |
| 分子式 | C12H11N3O4 | 分子量 | 261.23 |
| 溶解度 | DMSO : 4 mg/mL (15.31 mM; ultrasonic and warming and heat to 60°C) | 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 | 3.828 mL | 19.1402 mL | 38.2804 mL |
| 5 mM | 0.7656 mL | 3.828 mL | 7.6561 mL |
| 10 mM | 0.3828 mL | 1.914 mL | 3.828 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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。
1. 首先保证母液是澄清的；
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Selective block of recombinant glur6 receptors by NS-102, a novel non-NMDA receptor antagonist
Eur J Pharmacol 1994 Sep 15;269(1):43-9.PMID:7828657DOI:10.1016/0922-4106(94)90024-8.
The diversity of neuronal glutamate receptors continues to increase with the discovery of multiple subunits and subunit families. The significance of this potential receptor heterogeneity is unknown because pharmacological tools that could clearly distinguish between different structural isoforms have not yet been identified. A novel glutamate receptor antagonist, 5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime (NS-102), has been shown previously to selectively block the low affinity [3H]kainate binding site in rat brain. We have examined the effect of NS-102 on receptors expressed in fibroblasts from either glur6 subunits or a combination of glurB and glurD (glurB/D receptors). NS-102 (3 microM) reduced currents mediated by glur6 receptors and had very little effect on currents mediated by glurB/D receptors. The binding of [3H]kainate to glur6 receptors showed properties similar to those of the brain low affinity [3H]kainate binding site, and NS-102 inhibited specific binding to glur6 receptors with a potency nearly identical to those sites in brain membranes. Our findings suggest that NS-102 will be useful in identifying the functional role of native receptors containing a glur6 subunit.
A novel non-NMDA receptor antagonist shows selective displacement of low-affinity [3H]kainate binding
Eur J Pharmacol 1993 Aug 15;246(3):195-204.PMID:8223944DOI:10.1016/0922-4106(93)90031-4.
5-Nitro-6,7,8,9-tetrahydrobenzo[G]indole-2,3-dione-3-oxime (NS-102), a new competitive glutamate receptor antagonist displaced binding to non-N-methyl-D-aspartate (non-NMDA) binding sites with no activity at the NMDA and strychnine-insensitive glycine binding sites. Under experimental conditions in which both high- and low-affinity sites were labelled, NS-102 only partially inhibited the binding of [3H]kainate. Studies of NS-102 displacement of high-affinity versus low-affinity [3H]kainate binding showed a high selectivity of NS-102 for the low-affinity [3H]kainate binding site (Ki = 0.6 microM) compared to the high-affinity [3H]kainate binding site (Ki > 10 microM). NS-102 was a relatively weak inhibitor of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) binding (IC50 = 7.2 microM). NS-102 and related compounds with similar pharmacological profiles may become valuable tools in the characterization of the functional importance of the low-affinity [3H]kainate binding site.
Domoic acid neurotoxicity in hippocampal slice cultures
Amino Acids 2002;23(1-3):37-44.PMID:12373516DOI:10.1007/s00726-001-0107-5.
The neurotoxicity of domoic acid was studied in 2-3 week old rat hippocampal slice cultures, derived from 7 day old rat pups. Domoic acid 0.1-100 microM was added to the culture medium for 48 hrs, alone or together with the glutamate receptor antagonists NS-102 (5-Nitro-6,7,8,9-tetrahydrobenzo[G]indole-2,3-dione-3-oxime), NBQX (2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline) or MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate), followed by transfer of the cultures to normal medium for additional 48 hrs. Neuronal degeneration in the fascia dentata (FD), CA3 and CA1 hippocampal subfields was monitored and EC(50) values estimated by densitometric measurements of the cellular uptake of propidium iodide (PI). The CA1 region was most sensitive to domoic acid, with an EC(50) value of 6 microM domoic acid, estimated from the PI-uptake at 72 hrs. Protective effects of 10 microM NBQX against 3 and 10 microM domoic acid were observed for both dentate granule cells and CA1 and CA3c pyramidal cells. NS102 and MK 801 only displayed protective effects when combined with NBQX. MK801 significantly increased the combined neuroprotective effect of NBQX and NS102 against 10 microM domoic acid in both CA1 and FD, but not in CA3. We conclude, that domoic acid neurotoxicity in CA3 and in hippocampal slice cultures in general primarily involves AMPA/kainate receptors. At high concentrations (10 microM domic acid) NMDA receptors are, however, also involved in the toxicity in CA1 and FD.
Sevoflurane activates hippocampal CA3 kainate receptors (Gluk2) to induce hyperactivity during induction and recovery in a mouse model
Br J Anaesth 2017 Nov 1;119(5):1047-1054.PMID:28981700DOI:10.1093/bja/aex043.
Background: In addition to general anaesthetic effects, sevoflurane can also induce hyperactive behaviours during induction and recovery, which may contribute to neurotoxicity; however, the mechanism of such effects is unclear. Volatile anaesthetics including isoflurane have been found to activate the kainate (GluK2) receptor. We developed a novel mouse model and further explored the involvement of kainate (GluK2) receptors in sevoflurane-induced hyperactivity. Methods: Maximal speed, mean speed, total movement distance and resting percentage of C57BL/6 mice were quantitatively measured using behavioural tracking software before and after sevoflurane anaesthesia. Age dependence of this model was also analysed and sevoflurane-induced hyperactivity was evaluated after intracerebral injection of the GluK2 receptor blocker NS-102. Neurones from the hippocampal CA3 region were used to undertake in vitro electrophysiological measurement of kainate currents and miniature excitatory postsynaptic potential (mEPSP). Results: Sevoflurane induced significant hyperactivities in mice under sevoflurane 1% anaesthesia and during the recovery period, characterized as increased movement speed and total distance. The hyperactivity was significantly increased in young mice compared with adults (P<0.01) and pre-injection of NS-102 significantly prevented this sevoflurane-induced hyperactivity. In electrophysiological experiments, sevoflurane significantly increased the frequency of mEPSP at low concentrations and evoked kainate currents at high concentrations. Conclusions: We developed a behavioural model in mice that enabled characterization of sevoflurane-induced hyperactivity. The kainate (GluK2) receptor antagonist attenuated these sevoflurane-induced hyperactivities in vivo, suggesting that kainate receptors might be the underlying therapeutic targets for sevoflurane-induced hyperactivities in general anaesthesia.
(S)-5-fluorowillardiine-mediated neurotoxicity in cultured murine cortical neurones occurs via AMPA and kainate receptors
Eur J Pharmacol 1996 Oct 24;314(1-2):249-54.PMID:8957243DOI:10.1016/s0014-2999(96)00633-4.
We have examined the neurotoxic effects of kainate, (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and the novel AMPA-receptor preferring agonist (S)-5-fluorowillardiine in murine cultured cortical neurones. Kainate induced > 90% cell death (EC50 65 microM) and (S)-AMPA only about 50% cell death (EC50 3.1 microM), both in a monophasic dose-dependent manner. (S)-5-Fluorowillardiine also killed > 90% of neurones, however, in a biphasic dose-dependent manner (EC50 0.70 and 170 microM). Additionally, the neurotoxic effects of (S)-AMPA and (S)-5-fluorowillardiine (high-affinity component) were attenuated by the AMPA receptor antagonists LY293558 ((3,S,4aR, 6R,8aR)-6[2h91 H-tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinol ine- 3-carboxylic acid). A component of kainate and (S)-5-fluorowillardiine (low-affinity component) neurotoxicity was blocked by the low-affinity kainate receptor antagonist NS-102 (5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime). We have shown that both kainate and (S)-AMPA can effect substantial cell death in cortical neurones and that the novel agonist (S)-5-fluorowillardiine exerts its excitotoxicity through both AMPA- and kainate-preferring receptors.